Skip to main content
PMC home page
Wiley Open Access Collection logoLink to Wiley Open Access Collection
. 2019 Oct 30;59(4):406–411. doi: 10.1111/ijd.14695

IL‐17 and its role in inflammatory, autoimmune, and oncological skin diseases: state of art

Nicoletta Bernardini 1,✉, Nevena Skroza 1, Ersilia Tolino 1, Alessandra Mambrin 1, Alessia Anzalone 1, Veronica Balduzzi 1, Daniela Colapietra 1, Anna Marchesiello 1, Simone Michelini 1, Ilaria Proietti 1, Concetta Potenza 1
PMCID: PMC7216999  PMID: 31663126

Abstract

Recent data support the theory of the involvement of IL‐17 in the pathogenesis of several chronic inflammatory skin diseases (psoriasis, atopic dermatitis, acne, hidradenitis suppurativa) and autoimmune skin diseases (alopecia areata, vitiligo, bullous diseases). Even if the role of IL‐17 in inflammatory and autoimmune diseases has been reported extensively, its role in tumor is still controversial. Some reports show that Th17 cells eradicate tumors, while others reveal that they promote the initiation and early growth of tumors. Herein, we review the role of IL‐17 in the involvement of some common dermatologic diseases: psoriasis, atopic dermatitis, hidradenitis suppurativa, acne, vitiligo, melanoma, and nonmelanoma skin cancers.

Introduction

IL‐17 is a cytokine whose family consists of six members, from IL‐17A to IL‐17F, even if the term IL‐17 usually refers to IL‐17A.1 All the family members share some activities: IL‐17A, IL‐17F, and their heterodimers IL‐17A/F have inflammatory effect with different strength; IL‐17B, IL‐17C, IL‐17D are proinflammatory cytokines with unknown role. The IL‐17E cytokine, also named IL‐25, is involved in Th2 cells response.2

Production of IL‐17 is mainly operated by T helper type 17 (Th17), CD8+ T cells, γδ T cells, invariant natural killer T cells (iNKT), natural killer (NK) cells, natural Th17 cells, and lymphoid tissue inducer (LTi) cells.1

IL‐17 exerts many physiological functions including: neutrophil recruitment, Th2 stimulation to provide an effective response against extracellular organisms, macrophage production of IL‐1β and TNF‐α, and inflammatory mediator matrix metalloproteinases (MMPs) induction.1

Despite of the important role of IL‐17 cytokine in regulating adaptive and innate immune systems,3 its overproduction could be involved in several diseases.4

In recent years, different studies have tried to associate the IL‐17 pathway to an increasing number of inflammatory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), lupus, polymyalgia rheumatica, giant cell arteritis, Behçet disease, dry‐eye syndrome, Sjögren's syndrome, Crohn's disease, and multiple sclerosis. However, the role of IL‐17 is still unclear.4 Th17 cells and IL‐17 have also been identified to be implicated in the pathogenesis of several human autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, systemic sclerosis, primary Sjogren's syndrome, alopecia areata, and vitiligo.5 Furthermore, a recent study reported a correlation between the serum levels of IL‐17 and activity of the disease in selected autoimmune bullous skin diseases, such as dermatitis herpetiformis (DH), bullous pemphigoid (BP), and pemphigus vulgaris (PV).6

Even though the role of IL‐17 in inflammatory and autoimmune diseases has been reported extensively, its role in tumors is still controversial.7

In an attempt to contribute to the description of the relationship between IL‐17 pathways and the most frequent dermatological diseases, we report the state of the art about the role of IL‐17 in psoriasis, atopic dermatitis, acne, hidradenitis suppurativa, vitiligo, alopecia areata, nonmelanoma skin cancer, and melanoma.

IL‐17 and Inflammatory Skin Diseases

Psoriasis

Recent evidences highlighted the importance of IL‐17A in the pathogenesis of psoriasis and psoriatic arthritis. IL‐17A upregulates the expression of inflammation‐related genes in keratinocytes and fibroblasts, resulting in the production of inflammatory cytokines, chemokines, and other mediators and the consequent clinical features.8

Linag et al. support the emergent role of IL‐17 in psoriasis pathogenesis, proving its effects on keratinocyte cultures to increase the expression of antimicrobial peptides (e.g. S100) and chemokines (e.g. CCL20) that activate and recruit neutrophils and T cells.9 Recent data reported a serum increase of IL‐17 in psoriatic patients.10 The IL‐17 binding to its receptor (IL‐17R) expressed by keratinocytes promotes the aberrant differentiation and proliferation of keratinocytes, the expression of chemokines (CXCL1, CXCL2, and CCL20) which enhance recruitment of Th17 and dendritic cells to the skin, the expression of antimicrobial peptides, and reduces the expression of cell adhesion molecules, resulting in disruption of skin barrier function.11

Zhang et al. in a recent work on a pediatric population reported a significantly higher frequency of Th17 and its cytokines in psoriatic patients' blood compared with healthy controls, pointing out a significantly positively relation between the increase of Th17 blood frequency and patient PASI.12 Likewise, Sofen et al. and Chiricozzi et al. reported a significant correlation between IL‐17 serum levels and disease severity, while Yilmaz et al. found an increase in IL‐17 in serum of patients with PASI > 10 more than patients with PASI < 10.13, 14, 15 Different authors have studied the correlation between serum levels of IL‐17 or its tissue expression and the clinical subtype of psoriasis or disease state.16, 17 Recently, the central role of IL‐17 in systemic inflammation and cardiovascular comorbidity in psoriasis patients has also been highlighted.18, 19, 20

Finally, the evidence of the role of IL‐17 in the pathogenesis of psoriasis has been supported by the proven efficacy of the treatment with anti‐IL‐17 in psoriatic patients.8, 21, 22

In particular, the biological agent brodalumab proved its efficacy and safety in generalized pustular psoriasis.23

Atopic dermatitis

The central role of cytokines in the pathogenesis of atopic dermatitis (AD) has been widely highlighted. Interleukin‐4 and interleukin‐13 are major causes of inflammation and itch in patients.24 Recently, the role of Th17 cells and IL‐17 in the pathogenesis of AD has been investigated. Th17 cells play a potential role in the immune activation, including attraction of neutrophils.25 An increase in IL‐17A, IL‐17E, IL‐17F, and IL‐23 serum concentrations has been demonstrated in children suffering from AD, which correlated with disease severity.26 Elevated IL‐17A and IL‐17E levels were found in the papillary dermis of AD lesions, especially in the acute phase.27 In AD mouse models, IL‐17E is upregulated inducing the expression of endothelin‐1, which is an important factor in developing pruritus.28 IL‐17E may be responsible for skewing the immune response to a Th2 dominance and decreases filaggrin production in keratinocytes, resulting in disorders of keratinization and an impaired skin barrier function/homeostasis.29 Considering the role of IL‐17 in the pathogenesis of DA, it is reasonable to speculate a possible effectiveness of anti‐IL‐17 in the treatment of AD. As anti‐IL‐17A therapy in psoriasis increases the risk of neutropenia and skin and oral candida infections, it seems reasonable to be cautious, as AD patients are more prone to skin and mucosal infections than patients suffering from psoriasis.30

Acne

The evidence of the presence of inflammatory factors in the very earliest stages of acne lesion prior to hyperproliferation of the follicular epithelium raises questions on the primary key role of inflammation in the pathogenesis of acne.31

Recently, the role of Th17 in acne lesions is under investigation. Examination of inflammatory changes in early acne lesions in two separate patient cohorts revealed a significant overexpression of cytokines involved in Th17 pathways.32 Agak et al. confirmed these findings, demonstrating the ability of P. acnes in inducing both Th17 and Th1 responses as measured, respectively, by IL‐17 and INF‐ɤ in human peripheral blood mononuclear cells (PBMCs) in vitro, as well as the expression of Th17 differentiation markers including RORα, RORc, and IL‐17RA and IL‐17RC.33 Moreover, at immunohistochemical examination, IL‐17 expressing cells were detectable only in the epidermis of acne patients. CD4+CD25+Foxp3+ regulatory T‐cells (T‐regs), a population linked to Th17 cells, are significantly increased in acne lesions. The differentiation of both Th17 cells and T‐regs depends on the cytokines present in the environment.34

In a recent study, Kistowska et al. suggested that acne may be a Th17‐mediated disease because P. acnes is a potent inducer of IL‐17 and IFN‐gamma from CD4+ T cells and that IL‐17+ cells were present in perifollicular infiltrates in biopsy samples of inflammatory acne lesions.35

Another study has highlighted some therapeutic implications of the Th17 pathway in patients with acne.36 Some drugs, such as dihydroxyvitamin D3, retinoids, vitamin A, and zinc, could have a successful role in the treatment of acne because of their inhibition of inflammatory Th17 and promotion of T‐reg responses.37

Hidradenitis suppurativa

Recent research focused on the inflammatory mechanisms involved in HS, suggesting a key role for immune dysregulation in its pathogenesis. Schlapbach et al. investigating the expression and cellular source of IL‐12, IL‐23, and IL‐17 in lesional skin reported that IL‐17 and IL‐23, which play a central role in the regulation of Th17 cells, were highly expressed.38 Van der Zee et al., comparing the cytokine levels in lesional HS skin biopsies after 24 hours of culture with the levels in healthy skin, showed that levels of IL‐1β, TNF‐α IL‐6, and IL‐17 were elevated in HS lesions.39 Similarly, Kelly et al. reported that the mRNA expression of IL‐17A, IL‐1β, TNFα, and IL‐10 is enhanced in lesional skin. In addition, they showed a significant enhancement of IL‐17A in uninvolved skin of patients with HS 10 cm away from any lesional activity.40 Based on these data, the abnormal expression of IL‐17 and its associated cytokine detected in lesional skin and uninvolved skin supported the hypothetical role of Th17 in lesion development. Likewise, Lima et al. demonstrated that the Th17 cells and neutrophils are significantly increased in lesional and perilesional skin with homogeneous distribution in the perifollicular region.41 The evidences supporting the role of IL‐17 in the pathogenesis of HS provided a rationale for treating hidradenitis with anti‐IL‐17 antibodies, especially in case of HS refractory to local and systemic antibiotic therapy as well as other biological drugs.42

IL‐17 and Autoimmune Skin Diseases

Vitiligo

Several human studies have investigated the roles that Th17 cells play in vitiligo, demonstrating an increased frequency of circulating Th17 cells and elevated serum levels of IL‐17 that positively correlates with disease duration, extent, and severity of disease.43

In a recent study, Kotobuki et al. confirmed the presence of Th17 cell infiltration in vitiligo skin and speculated that Th17 cells do not exert a direct effect on the melanocytes but by producing cytokines.44 Therefore, the presence of a cytokine network and the secretion of IL‐17A from Th17 cells may represent a new mechanism underlying the pathogenesis of vitiligo.

Assessing the role of IL‐17 in the pathogenesis of vitiligo, Bassiouny et al. demonstrated elevated IL‐17 levels in lesional skin, while Basak et al. showed a positive correlation between serum IL‐17 levels and the extent of the depigmentation area in vitiligo.45, 46

Evaluating the frequencies of peripheral blood Th17 cells and serum levels of IL‐17A and Th17 cell‐related cytokines in 45 patients with NSV, Zhou et al. showed increased circulating Th17 cells as well as elevated serum IL‐17A, TGF‐β1, and IL‐21 levels in NSV patients, suggesting their potential involvement in the development and progression of NSV.47 These data supported the evidence that Th1 and Th17 played an important role in cellular immunity in the progression of vitiligo.

Further clinical studies are needed to confirm this correlation and to determine the implications of directly targeting the IL‐17 pathway in order to treat vitiligo.

Alopecia areata

Recent evidences highlighted the role of both Th17 cells and T regulatory (Treg) cells in the pathogenesis of alopecia areata (AA).48, 49 Loh et al. carried out a study in order to determine whether AA is associated with alterations in lesional and serum Th17 and Treg cytokines. Studying scalp biopsies and serum samples from AA patients, they found out that lesional IL‐17, IL‐22, and serum IL‐1, IL‐17, TNF‐α, and TGF‐β were significantly higher in AA patients than in controls. Moreover, they demonstrated that there were positive correlations between lesional and serum IL‐17 and disease severity.48

A similar result has been demonstrated recently in another study which found higher serum IL‐17 level in patients with AA than in control subjects. In particular, El‐Morsy et al. revealed significantly higher serum IL‐17A levels in patients aged ≤30 years compared with those aged >30 years. This significant negative correlation between patient age and serum IL‐17A was not detected in the control group.49 With regard to the association among IL‐17A levels and gender, age, disease duration, subtype, or number of patches, Atwa et al. found that the concentrations of IL‐17 are associated with disease severity and are different according to the clinical phenotype being lowest in patients with only one patch of hair loss and highest in alopecia universalis/totalis.50

Tanemura et al., performing immunofluorescent study of alopecia lesions, detected a significant infiltration of CD4+ IL‐17A+ Th17 cells in the dermis, particularly around hair follicles, suggesting the involvement of Th17 cells in the pathogenesis of AA.51

These results provide evidence on a functional role of TH17 and IL‐17 in the pathogenesis of AA and highlighted the potential therapeutic role by targeting Th17 cytokines for the treatment of AA.

IL‐17 and Oncological Skin Diseases

NMSC

Besides other features, Th17 cells are characterized by pro‐ or antitumorigenic properties depending on the stimuli of the microenviroment.7 Some reports showed that Th17 cells eradicate tumors, while others revealed that they promote the initiation and early growth of tumors.52 The microenvironment can exert inhibitory effects on malignant cells, but tumors can circumvent these inhibitory signals and use the surrounding cells for their own survival, causing growth, invasion, and metastasis. The generation of Th17 cells with different phenotypes in response to tumor microenvironment would explain the conflicting observations.7

One evident role of Th17 cells in tumor progression is their contribution to local inflammation. Cytokines produced by inflammatory Th17 cells stimulate inflammation‐dependent tumor growth by promoting angiogenesis and by suppressing antitumor immunity.53 Particularly regarding NMSC, Nardinocchi et al. investigated the role of IL‐17 and IL‐22 in the growth and invasiveness of human skin basal‐cell carcinoma (BCC) and squamous‐cell carcinoma (SCC). They showed that both tumor types are infiltrated with a high number of IL‐17+ and IL‐22+ T lymphocytes. In vitro studies demonstrated that IL‐17 increased the proliferation and migration of the BCC‐ and SCC‐cell lines M77015 and CAL27. This study, demonstrating a pro tumorigenic role of IL‐17 in human SCCs and BCCs, suggested treatment with anti‐IL‐17 antibodies as a therapeutic approach in selected cases.54

In addition, an Italian group investigated changes of expression of IFN‐γ, IL‐17, IL‐23, and IL‐22 cytokines in BCC and their modulation during imiquimod (IMQ) treatment or photodynamic therapy (PDT). Increased levels of IFN‐γ, IL‐17, IL‐23, and IL‐22 were found in BCCs compared to normal skin, and their expression results correlated with the severity of the inflammatory infiltrate. Moreover, IL‐17 was increased in nodular forms. Finally, they highlighted an increase of IFN‐γ, IL‐23, and IL‐22, IL‐17 because of early inflammatory response induced by IMQ and PDT treatment.55

These findings confirm the role of Th17 and related cytokines in NMSC pathogenesis and in the inflammatory response during therapies.

Melanoma

The role of Th17 and IL‐17 in melanoma is complex, as it has been reported in NMSC. Effects of Th17 and IL‐17 in murine models of cancer has been investigated, showing that Th17 cells activate endogenous cytotoxic CD8+ T cells and eradicate melanoma in mice.56 Muranski et al. reported that Th17‐polarized cells better mediated destruction of advanced B16 melanoma, and their therapeutic effect was critically dependent on interferon (IFN) production.57 In murine B16 melanoma, it has been shown that the tumor‐promoting role of IL‐17 has a direct effect on tumor cells through an IL‐6‐Stat3 signaling pathway.58

Recently, Jun Li et al. demonstrated that IL‐7/IL‐7R‐Stat3‐IL‐17 pathway promotes melanoma growth, and its inhibition may contribute to tumor growth in murine models of melanoma.59

Based on these evidences, Ganzetti et al. have speculated that this model could be reproducible in human cutaneous melanoma. They studied the expression of interleukin‐17 (IL‐17), IL‐23, and p73 in 35 malignant melanomas comparing them with benign melanocytic nevi and Spitz nevi. Their results showed a greater IL‐17 and IL‐23 immunohistochemistry expression in the melanoma group than in ordinary benign nevi.60 These results could suggest a possible IL‐17, IL‐23, and p73 involvement in cutaneous melanomas with a hypothetical impact on melanoma invasiveness.

It has been hypothesized that IL‐17 may stimulate cancer cells to produce some angiogenic factors (VEGF), thereby enhancing tumor angiogenesis.58 These results could suggest a direct impact on the biological behavior of tumor cells in the local microenvironment and could explain the increased expression of VEGF and angiogenesis in invasive melanomas.

In patients with advanced inoperable melanoma, a better understanding of the regulation of cytokine and cellular immune activity in response to melanoma may be important in order to predict therapeutic response to immunotherapy, including treatment with ipilimumab. A recent study showed that in patients with regionally advanced melanoma enrolled in a trial of neoadjuvant therapy with ipilimumab at 10 mg/kg, baseline IL‐17 level was significantly associated with the risk of subsequent development of severe immune‐mediated diarrhea/colitis.61 Further investigation and confirmation in larger trials is necessary in order to confirm these findings.

Conclusion

We reported a global up‐to‐date overview about the role of IL‐17 in inflammatory, autoimmune, and oncological skin diseases. The literature data suggest that this cytokine has been implicated in these diseases with different pathways. It could be hypothesized that IL‐17 might represent a link between different diseases underlying a common pathogenic basis where inflammation could be considered the distinctive benchmark and this cytokine as a marker. Further clinical studies are needed to confirm this correlation and to determine its implications for the development of new therapeutic approaches as well as the monitoring of disease activity and therapeutic response.

Questions (answers provided after references)

  1. All the family members of IL‐17 family have an inflammatory effect.

  2. The pathogenetic mechanisms triggered by the binding of IL‐17 with its receptor in patients with psoriasis result in disruption of skin barrier function.

  3. There is no evidence about the efficacy of treatment with anti‐IL‐17 in psoriatic patients.

  4. Psoriatic patients are more prone to skin and mucosal infections than patients suffering from atopic dermatitis.

  5. Some drugs, such as dihydroxyvitamin D3, retinoids, vitamin A, and zinc, have a successful role in the treatment of acne because of their inhibition of inflammatory Th17.

  6. In the case of HS refractory to antibiotic therapy or other biological drugs, there is evidence that supports the role of IL‐17 in the pathogenesis of HS and provides a rationale for treating hidradenitis with anti‐IL‐17.

  7. In a recent study, is it confirmed that Th17 cells exert a direct effect on melanocytes.

  8. Is it demonstrated that the concentrations of IL‐17 are associated with disease severity and are different according to the clinical phenotype.

  9. Th17 cells are characterized by pro‐ or anti‐tumorigenic properties depending on the stimuli of the microenvironment.

  10. Better understanding of the regulation of IL‐17 and cellular immune activity in response to melanoma to predict therapeutic response to immunotherapy could be an advantage for patients with advanced inoperable melanoma.

Answers to questions

  1. True

  2. True

  3. False

  4. False

  5. True

  6. True

  7. False

  8. True

  9. True

  10. True

Funding: None.

Conflict of interest: None.

[Correction added on March 05, 2020 after first online publication: the copyright line has been changed.]

References

  • 1. Amatya N, Garg AV, Gaffen SL. IL‐17 signaling: the yin and the yang. Trends Immunol 2017; 38: 310–322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Gaffen SL. Structure and signalling in the IL‐17 receptor family. Nat Rev Immunol 2009; 9: 556–567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. Sharma J, Balakrishnan L, Datta KK, et al A knowledgebase resource for interleukin‐17 family mediated signaling. J Cell Commun Signal 2015; 9: 291–196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. Beringer A, Noack M, Miossec P. IL‐17 in chronic inflammation: from discovery to targeting. Trends Mol Med 2016; 22: 230–241. [DOI] [PubMed] [Google Scholar]
  • 5. Maddur MS, Miossec P, Kaveri SV, et al Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies. Am J Pathol 2012; 576: 8–18. [DOI] [PubMed] [Google Scholar]
  • 6. Żebrowska A, Woźniacka A, Juczyńska K, et al Correlation between IL36α and IL17 and activity of the disease in selected autoimmune blistering diseases. Mediators Inflamm 2017; 2017: 1–10. 10.1155/2017/8980534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Bailey SR, Nelson MH, Himes RACM, et al Th17 cells in cancer: the ultimate identity crisis. Front Immunol 2014; 17: 276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Kirkham BW, Kavanaugh A, Reich K. Interleukin‐17A: a unique pathway in immune‐mediated diseases: psoriasis, psoriatic arthritis and rheumatoid arthritis. Immunology 2014; 141: 133–142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Linag SC, Tan XY, Luxenberg DP, et al Interleukin (IL)‐22 and IL‐17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 2006; 203: 2271–2279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Fotiadou C, Lazaridou E, Sotiriou E, et al IL‐17A, IL‐, 22, and IL‐23 as markers of psoriasis activity: a cross‐sectional, hospital‐ based study. J Cutan Med Surg 2015; 19: 555–560. [DOI] [PubMed] [Google Scholar]
  • 11. Alunno A, Carubbi F, Cafaro G, et al Targeting the IL‐23/IL‐17 axis for the treatment of psoriasis and psoriatic arthritis. Expert Opin Biol Ther 2015; 15: 1727–1737. [DOI] [PubMed] [Google Scholar]
  • 12. Zhang L, Li Y, Yang X, et al Characterization of Th17 and FoxP3+ Treg cells in pediatric psoriasis patients. Scand J Immunol 2016; 83: 174–180. [DOI] [PubMed] [Google Scholar]
  • 13. Sofen H, Smith S, Matheson RT, et al Guselkumab (an IL‐23‐speci‐ fic mAb) demonstrates clinical and molecular response in patients with moderate‐to‐severe psoriasis. J Allergy Clin Immunol 2014; 133: 1032–1040. [DOI] [PubMed] [Google Scholar]
  • 14. Chiricozzi A, Suarez‐Farinas M, Fuentes‐Duculan J, et al Increased expression of interleukin‐17 pathway genes in nonlesional skin of moderate‐to‐severe psoriasis vulgaris. Br J Dermatol 2016; 174: 136–145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Yilmaz SB, Cicek N, Coskun M, et al Serum and tissue levelsof IL‐17 in different clinical subtypes of psoriasis. Arch Dermatol Res 2012; 304: 465–469. [DOI] [PubMed] [Google Scholar]
  • 16. Lee E, Zarei M, La Senna C, et al Psoriasis targeted therapy: characterization of interleukin 17A expression in subtypes of psoriasis. J Drugs Dermatol 2015; 14: 1133–1136. [PubMed] [Google Scholar]
  • 17. Roh NK, Han SH, Youn HJ, et al Tissue and serum inflammatory cytokine levels in korean psoriasis patients: a comparison between plaque and guttate psoriasis. Ann Dermatol 2015; 27: 738–743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. Proietti I, Raimondi G, Skroza N, et al Cardiovascular risk in psoriatic patients detected by heart rate variability (HRV) analysis. Drug Dev Res 2014; 75: 81–84. [DOI] [PubMed] [Google Scholar]
  • 19. Coimbra S, Oliveira H, Neuparth MJ, et al Systemic inflammation and proinflammatory interleukin‐17 signalling persist at the end of therapy in patients with metabolic syndrome and psoriasis, reducing the lenght of remission. Br J Dermatol 2016; 174: 414–416. [DOI] [PubMed] [Google Scholar]
  • 20. Boehncke WH. Systemic inflammation and cardiovascular comorbidity in psoriasis patients: causes and consequences. Front Immunol 2018; 9: 579 10.3389/fimmu.2018.00579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Wang EA, Suzuki E, Maverakis E, et al Targeting IL‐17 in psoriatic arthritis. Eur J Rheumatol 2017; 4: 272–277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Diotallevi F, Campanati A, Radi G, et al Ixekizumab for treatment of moderate to severe plaque psoriasis: real world clinical experience. G Ital Dermatol Venereol 2018; 9 10.23736/S0392-0488.18.06094-7. [DOI] [PubMed] [Google Scholar]
  • 23. Reich A. Interleukin‐17 blockade in generalized pustular psoriasis‐new hope for severely ill patients. Br J Dermatol 2017; 176: 572–573. [DOI] [PubMed] [Google Scholar]
  • 24. Sayaseng KY, Vernon P. Pathophisiology and management of mild to moderate pediatric atopic dermatitis. J Pediatr Health Care 2018; 32: S2–S12. [DOI] [PubMed] [Google Scholar]
  • 25. Nograles KE, Zaba LC, Guttman‐Yassky E, et al Th17 cytokines interleukin (IL)‐ 17 and IL‐22 modulate distinct inflammatory and keratinocyte‐response pathways. Br J Dermatol 2008; 159: 1092–1102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Leonardi S, Cuppari C, Manti S, et al Serum interleukin 17, interleukin 23, and interleukin 10 values in children with atopic eczema/dermatitis syndrome (AEDS): association with clinical severity and phenotype. Allergy Asthma Proc 2015; 36: 74–81. [DOI] [PubMed] [Google Scholar]
  • 27. Koga C, Kabashima K, Shiraishi N, et al Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Dermatol 2008; 128: 2625–2630. [DOI] [PubMed] [Google Scholar]
  • 28. Aktar MK, Kido‐Nakahara M, Furue M, et al Mutual upregulation of endothelin‐1 and IL‐25 in atopic dermatitis. Allergy 2015; 70: 846–854. [DOI] [PubMed] [Google Scholar]
  • 29. Hvid M, Vestergaard C, Kemp K, et al IL‐25 in atopic dermatitis: a possible link between inflammation and skin barrier dysfunction? J Invest Dermatol 2011; 131: 150–157. [DOI] [PubMed] [Google Scholar]
  • 30. Nygaard U, Vestergaard C, Deleuran M. Emerging treatment options in atopic dermatitis: systhemic therapies. Dermatology 2017; 233: 344–357. [DOI] [PubMed] [Google Scholar]
  • 31. Jeremy AH, Holland DB, Roberts SG, et al Inflammatory events are involved in acne lesion initiation. J Invest Dermatol 2003; 21: 20–27. [DOI] [PubMed] [Google Scholar]
  • 32. Kelhala HL, Palatsi R, Fyhrquist N, et al IL‐17, Th17 pathway is activated in acne lesions. PLoS ONE 2014; 9: e105238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. Agak GW, Qin M, Nobe J, et al Propionibacterium acnes Induces an IL‐17 response in acne vulgaris that is regulated by vitamin A and vitamin D. J Invest Dermatol 2014; 134: 366–373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34. Korn T, Bettelli E, Oukka M, et al IL‐17 and Th17 cells. Annu Rev Immunol 2009; 27: 485–517. [DOI] [PubMed] [Google Scholar]
  • 35. Kistowska M, Meier B, Proust T, et al Propionibacterium acnes promotes Th17 and Th17/Th1 responses in acne patients. J Invest Dermatol 2015; 135: 110–118. [DOI] [PubMed] [Google Scholar]
  • 36. Sardana K, Verma G. Propionibacterium acnes and the Th1/Th17 Axis, implications in acne pathogenesis and treatment. Indian J Dermatol 2017;62:392–394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. Xiao S, Jin H, Korn T, et al Retinoic acid increases Foxp3+ regulatory T cells and inhibits development of Th17 cells by enhancing TGF‐beta‐driven Smad3 signaling and inhibiting IL‐6 and IL‐23 receptor expression. J Immunol 2008; 181: 2277–2284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Schlapbach C, Hanni T, Yawalkar N, et al Expression of the IL‐23/Th17 pathway in lesions of hidradenitis suppurativa. J Am Acad Dermatol 2011; 65: 790–798. [DOI] [PubMed] [Google Scholar]
  • 39. Van der Zee HH, de Ruiter L, Boer J, et al Alterations in leucocyte subsets and histomorphology in normal‐appearing perilesional skin and early and chronic hidradenitis suppurativa lesions. Br J Dermatol 2012; 166: 98–106. [DOI] [PubMed] [Google Scholar]
  • 40. Kelly G, Hughes R, McGarry T, et al Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa. Br J Dermatol 2015; 173: 1431–1439. [DOI] [PubMed] [Google Scholar]
  • 41. Lima AL, Karl I, Giner T, et al Keratinocytes and neutrophils are important sources of proinflammatory molecules in hidradenitis suppurativa. Br J Dermatol 2015; 174: 514–521. [DOI] [PubMed] [Google Scholar]
  • 42. Jørgensen AR, Yao Y, Thomsen SF. Therapeutic response to Secukinumab in a 36‐year‐old woman with Hidradenitis suppurativa. Case Rep Dermatol Med 2018; 16: 1–3. 10.1155/2018/8685136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43. Singh RK, Lee KM, Vujkovic‐Cvijin I, et al The role of IL‐17 in vitiligo: a review. Autoimmun Rev 2016; 15: 397–404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44. Kotobuki Y, Tanemura A, Yang L, et al Dysregulation of melanocyte function by Th17‐related cytokines: significance of Th17 cell infiltration in autoimmune vitiligo vulgaris. Pigment Cell Melanoma Res 2012; 25: 219–230. [DOI] [PubMed] [Google Scholar]
  • 45. Basak P, Adiloglu AK, Ceyhan AM, et al The role of helper and regulatory T cells in the pathogenesis of vitiligo. J Am Acad Dermatol 2009; 256–260. [DOI] [PubMed] [Google Scholar]
  • 46. Bassiouny DA, Shaker O. Role of interleukin‐17 in the pathogenesis of vitiligo. Clin Exp Dermatol 2011; 36: 292–297. [DOI] [PubMed] [Google Scholar]
  • 47. Zhou L, Shi YL, Li K, et al Increased circulating Th17 cells and elevated serum levels of TGF‐beta and IL‐21 are correlated with human nonsegmental vitiligo development. Pigment Cell Melanoma Res 2015; 28: 324–329. [DOI] [PubMed] [Google Scholar]
  • 48. Loh SH, Moon HN, Lew BL, et al Role of T‐helper 17 cells and T regulatory cells in alopecia areata: comparison of lesion and serum cytokine between controls and patients. J Eur Acad Dermatol Venereol 2017; 32: 1028–1033. [DOI] [PubMed] [Google Scholar]
  • 49. El‐Morsy EH, Eid AA, Ghoneim H, et al Serum level of interleukin‐17A in patients with alopecia areata and its relationship to age. Int J Dermatol 2016; 55: 869–874. [DOI] [PubMed] [Google Scholar]
  • 50. Atwa MA, Youssef N, Bayoumy NM. T‐helper 17 cytokines (interleukins 17,21,22 and and tumor necrosis factor‐α) in patients with alopecia areata: association with clinical type and severity. Int J Dermatol 2016; 55: 666–672. [DOI] [PubMed] [Google Scholar]
  • 51. Tanemura A, Oiso N, Nakano M, et al Alopecia areata: infiltration of Th17 cells in the dermis, particularly around hair follicles. Dermatology 2013; 226: 333–336. [DOI] [PubMed] [Google Scholar]
  • 52. Zou W, Restifo NP. T(H)17 cells in tumour immunity and immunotherapy. Nat Rev Immunol 2010; 10: 248–256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53. He D, Li H, Yusuf N, et al IL‐17 mediated inflammation promotes tumor growth and progression in the skin. PLoS ONE 2012; 7: e32126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54. Nardinocchi L, Sonego G, Passarelli F, et al Interleukin‐17 and interleukin‐22 promote tumor progression in human nonmelanoma skin cancer. Eur J Immunol 2015; 45: 922–931. [DOI] [PubMed] [Google Scholar]
  • 55. Pellegrini C, Orlandi A, Costanza G, et al Expression of IL‐23/Th17‐related cytokines in basal cell carcinoma and in response to medical treatments. Plos One 2017;12(8): e0183415 10.1371/journal.pone.0183415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56. Martin‐Orozco N, Muranski P, Chung Y, et al T helper 17 cells promote cytotoxic T cellactivation in tumor immunity. Immunity 2009; 31: 787–798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57. Muranski P, Boni A, Antony PA, et al Tumor‐specific Th17‐polarized cells eradicate large established melanoma. Blood 2008; 112: 362–373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58. Wang L, Yi T, Kortylewski M, et al IL‐17 can promote tumor growth through an IL‐6‐Stat3 signaling pathway. J Exp Med 2009; 206: 1457–1464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59. Li J, Liu J, Mao X, et al IL‐7 receptor blockade inhibits IL‐17‐producing γδ cells and suppresses melanoma development. Inflammation 2014; 37: 1444–1452. [DOI] [PubMed] [Google Scholar]
  • 60. Ganzetti G, Rubini C, Campanati A, et al IL‐17, IL‐23, and p73 expression in cutaneous melanoma: a pilot study. Melanoma Res 2015; 25: 232–238. [DOI] [PubMed] [Google Scholar]
  • 61. Tarhini AA, Zahoor H, Lin Y, et al Baseline circulating IL‐17 predicts toxicity while TGF‐β1 and IL‐10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma. J Immunother Cancer 2015; 15: 39. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from International Journal of Dermatology are provided here courtesy of Wiley

RESOURCES