Table 2.

Expert opinion characteristics and recommendations ^a .

Author, year	Institution/affiliation	Funding/Sponsor	Immune-resolution outcomes proposed/recommended	Authors’ conclusions
Asthma
Menzies-Gow, 2021 ( 16)	Royal Brompton Hospital, Respiratory Medicine. The Breathing Institute, Children’s Hospital Colorado. Department of Pediatrics, University of Colorado School of Medicine, Anschutz Medical Campus. Department of Medicine, Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin-Madison.	None	None	Biologics can achieve some but not all criteria for remission and efforts to develop treatments achieving full remission criteria still need to be sustained.
Gauvreau, 2020 ( 17)	Department of Medicine, McMaster University. Respiratory & Immunology, BioPharmaceuticals Medical. Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D.	AstraZeneca and Amgen	Thymic stromal lymphopoietin (TSLP) expression and biomarkers for patients who respond to TSLP therapy.	TSLP blockade could serve as an immunomodulatory function in asthma, restoring homeostatic balance.
Atopic Dermatitis
Kalamaha, 2019 ( 41)	Department of Internal Medicine, University of North Dakota School of Medicine and Health Sciences. Hematology and Medical Oncology, Sanford Health. Department of Pediatrics, University of North Dakota School of Medicine and Health Sciences. Allergy and Immunology, Sanford Health.	None	None. The authors stated that additional research was needed to better understand the pathogenesis of atopic dermatitis, and suggested that future research will likely focus on the modulation or inhibition of certain cytokines, particularly IL-4, IL-13, IL-17, IL-31, and JAK-signal transducer and activator of transcription (STAT) inhibition.	Several trials on the use of biologics for AD did not demonstrate long-term safety and efficacy. Future research should be directed to develop biomarkers for different AD phenotypes to allow for targeted therapy of AD.
Guttman-Yassky, 2013 ( 18)	National Jewish Health, Department of Pediatrics, Colorado.	National Institutes of Health grants R01 AR41256	Targeting T helper (Th)2 or Th22 (and the corresponding cytokines IL-4R and IL-22, respectively) simultaneously or sequentially might be needed to maximize effectiveness.	Validated biomarkers for disease improvement in AD are available and should be used to determine whether the clinical resolution of the disease is also accompanied by molecular and tissue resolution. This should help for the development of biologic therapies directed at pathways driving AD.
Rheumatoid Arthritis
Hemmatzadeh, 2022 ( 19)	Tabriz University of Medical Sciences. Immunology Research Center, Tabriz University of Medical Sciences Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences Department of Biology, Faculty of Natural Science, University of Tabriz Non‐Communicable Diseases Research Center, Alborz University of Medical Sciences Department of Immunology, School of Medicine, Alborz University of Medical Sciences Research Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences	Tabriz University of Medical Sciences	Potential markers/outcomes related to inhibitory and regulatory pathways, such as CTLA‐4, PD‐1/PD‐L1, BTLA, LAG3, TIM3, TIGIT, and VISTA.	Downmodulation of the molecules involved in the inhibitory and regulatory pathways, such as CTLA‐4, PD‐1/PD‐L1, BTLA, LAG3, TIM3, TIGIT, and VISTA by specific antibodies or recombinant proteins should be used in the future for controlling diseases mediated by disturbed T cell‐associated immune responses such as those seen in RA.
Carmona, 2018 ( 20)	Departamento de Genética e Instituto de Biotecnología, Universidad de Granada. Instituto de Parasitologia y Biomedicina Lopez-Neyra, Consejo Superior de Investigaciones Cientificas	Ramón y Cajal’ programme of the Spanish Ministry of Economy and Competitiveness (RYC-2014-16458); Instituto de Salud Carlos III (ISCIII), Spain, through the RETICS Program RD16/0012/0004 (RIER); and the EU/EFPIA Innovative Medicines Initiative Joint Undertaking PRECISESADS	PTPN22-encoded expression of lymphoid-specific tyrosine phosphatase (LYP)	PTPN22 encodes a LYP which is a master regulator of the immune response. Understanding and controlling the pathogenic implications of the PTPN22 risk alleles may help to achieve a complete remission of RA or at least to slow progression.
SLE
Akbarzadeh, 2023 ( 21)	Department of Rheumatology and Clinical Immunology, University of Lubeck	German Research Foundation (EXC2167)	Treg recovery and expansion maintained by IL-2	Low-dose IL-2 in combination with other immunotherapeutics including biologics provides synergistic and complementary immunomodulatory effects in SLE.
Nakayamada, 2022 ( 42)	The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health	Ministry of Health, Labor and Welfare of Japan, the Ministry of Education, Culture, Sports, Science and Technology of Japan (#JP20K08815, JSPS KAKENHI), and University of Occupational and Environmental Health (UOEH), Japan, through UOEH Grant for Advanced Research	Activation of innate immunity pathways stimulates the release of the cytokines BAFF, type I interferon, type II interferon, IL-12, and/or IL-23 and these activate acquired immunity pathways including T cell differentiation and activation, B-cell class switching, and differentiation into antibody-producing cells. Also, serum levels of soluble BAFF and IFN-α rise with increased disease activity.	The pathogenesis of SLE involves abnormalities in both acquired and innate immune systems linked to the action of various cytokines, and in turn to JAKs. This makes JAK inhibition a key potential treatment target in SLE.
Rheumatoid Arthritis and SLE
Iwata, 2021 ( 22)	The First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu.	JSPS (Japan Society for the Promotion of Science) grant number #JP16K09928	None. The authors considered various strands of evidence on mechanisms of metabolic regulation of B cells and other immune cells as potential treatment targets in rheumatoid arthritis and SLE but concluded that more research is needed on this area, without proposing specific measures by how immunoregulatory effects might best be assessed.	Although drugs that target mTOR, AMPK, and glycolytic systems such as sirolimus, rapamycin, and metformin have shown some efficacy and tolerability in clinical trials in patients with SLE, they have not led to major developments in therapeutic approaches. A better understanding of intrinsic immunometabolism mechanisms including those for B cells and other immune cells, is needed, and may aid the development of novel treatments for SLE.
Ulcerative Colitis and Asthma
Perucci, 2017 ( 23)	Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais. Programa de Pós-Graduação em Análises Clínicas e Toxicológicas, Universidade Federal de Minas Gerais. Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais	Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq (447452/2014-2) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais FAPEMIG (APQ-03318-15) fellowship	Markers of pro-resolving mechanisms, such as those involving alterations in the levels or function of mediators annexin A1 (ANXA1) and specialized pro-resolving lipid mediators (SPMs; e.g., arachidonic acid, n-6 PUFA)	The complex interplay between pro-resolving mediators such as ANXA1 and SPMs highlights the central role of immune resolution in tissue homeostasis. Evidence in asthma suggests that deficiencies of ANXA1 and LXA4 (an SPM) could occur early in disease progression. Also, ANXA1 and SPM-based interventions might represent novel therapeutic approaches for patients with asthma. Evidence in ulcerative colitis has suggested that there is deficient synthesis of LXA4 and that (as with ANXA1), LXA4 expression is increased in clinical remission. Such data indicate that SPM analogs might be potential candidate treatments for IBD.
Ulcerative Colitis
Porter, 2018 ( 43)	School of Medicine, Medical Sciences and Nutrition, University of Aberdeen. Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health	NR (details provided only of support received by some of the authors but not specifically for the reported study)	None. The authors discussed the relevance of B cells and Treg.	There is no universally effective treatment for IBD and current interventions do not induce lasting remission in all, and/or are associated with long-term adverse effects, which may be chronic. A personalized medicine approach is needed given the significant variability between patients with regard to disease activity, progression over time, and response to treatment.
Leiman, 2014 ( 44)	Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania.	NR	None. The authors highlighted targeting cellular adhesion (e.g., through vedolizumab) and inflammatory cell signaling as key strategies for the management of ulcerative colitis.	There is potential for new and effective therapies for patients with IBD. Vedolizumab is one such novel therapy for ulcerative colitis.

^aAll expert opinions were review articles and were from multiple specialists/commentators.

AD, atopic dermatitis; AMPK, adenosine-monophosphate-activated protein kinase; BAFF, B-cell–activating factor; BTLA, B-cell lymphocyte attenuator; CTLA-4, cytotoxic T-lymphocyte–associated antigen-4; IBD, inflammatory bowel disease; IFN, interferon; IL, interleukin; JAK, Janus kinase; LAG3, lymphocyte activation gene 3; mTOR, mammalian target of rapamycin; NR, not reported; PD-1, programmed cell death 1; PD-L1, programmed cell death-ligand 1; PTPN22, protein tyrosine phosphatase, non-receptor type 22; PUFA, polyunsaturated fatty acids; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; TIGIT, T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains; TIM3, T cell immunoglobulin and mucin domain 3; Treg, regulatory T-cells; VISTA, V-domain immunoglobulin suppressor of T cell activation.