Table 1.

Circulating blood cells involved in AR-associated inflammation

Cell Type	Subset	Main mediators	Established role	Findings in allergic rhinitis (AR)
T cells	Th2	• IL-4 • IL-5 • IL-13 • IL-10	• extracellular parasites • allergic inflammation	• nasal Th2 cytokine predominance • ↑ circulating Th2 cells in AR • ↓ circulating numbers after AIT
	Th9	• IL-9 • IL-10	• extracellular pathogens • allergic inflammation	• Th9 cytokines associated with nasal eosinophil infiltration and survival in mice • (↑) circulating Th9 cells in AR • (↓) circulating Th9 cells after AIT
	Th17	• IL-17A • IL-17F • IL-21 • IL-22 • CCL20	• extracellular bacteria • fungi • autoimmune disease	• Th17 cytokines associated with nasal eosinophil and neutrophil infiltration • ↑ serum IL-17A levels • (↑) circulating Th17 cells in AR • (↓) circulating Th17 numbers after AIT
	Th22	• IL-22	• proinflammatory and immune-modulating functions • wound healing • cell proliferation • anti-apoptosis	• correlation with clinical symptoms • ↑ circulating Th22 numbers in HDM AR
	Tfh	• IL-21	Promotion of • germinal center responses • B cell class switching	• IL-4 source (?) • inducer of Th2 cell responses • (↓) circulating Tfh cells in AR
	Cytotoxic T cell (Tc)	• perforin • protease • IFN-γ	• intracellular pathogens • induced cell apoptosis	• involved in atypical AR (?) • stimulate B cell IgE class switching • (↓) circulating Tc cells in AR • ↓ IL-4 producing subtype after AIT
	γδ T cell	• IFNγ • IL-17A • IL-17F • IL-22	• proinflammatory and immune-modulating functions at epithelial surfaces • innate and adaptive immunity participation	• yδT cytokines induce B cell IgE synthesis • support Th2 inflammatory response • oligoclonal proliferation in nasal mucosa (?) • ↑ circulating yδT cell percentages correlating with Th17 numbers in AR • negative correlation with Tregs
	Tr1	• IL-10	• immune-modulating	• inverse correlation with symptom scores • (↓) circulating Tr1 cells in AR
	Treg	• IL-10 • TGF-β • IL-35	• immune tolerance • immune modulatory • lymphocyte homeostasis	• ↑ Tregs in nasal mucosa after allergen exposure • ↨ circulating Treg numbers in AR • ↔ circulating Tregs 1 year after AIT
B cells	B cell		• antibody production • antigen presentation • IgE source in allergic disease	• circulating allergen-specific B cells show adaptive memory responses • isotype switching to IgE+ B cells in nasal mucosa through interactions with local dendritic and T cells (?) • (↓) circulating IgE+ B cells after AIT without IgE correlation
	Breg	• IL-10	• antibody production (↑IgG4) • immune modulation • IgG4 source in AIT	• ↓ circulating Bregs in AR especially in comorbid allergic asthma
Natural Killer Cells (NKs)	NK	• perforin • proteases • α-defensin	• cytotoxic • intracellular viruses • tumor cell clearance	• NK2 involved in effector cell chemotaxis (?) • ↑ circulating NK2 cells correlating with IgE levels in AR
	NK2	• IL-4 • IL-5 • IL-13
Innate Lymphoid Cells (ILCs)	ILC2	• IL-4 • IL-5 • IL-9 • IL-13	• allergic inflammation • atopic conditions	• nasal ILCs numbers associated with disease severity in AR • ↑ nasal ILC2 after allergen challenge in AR • (↑) circulating ILC2 percentages after allergen challenge in AR • ↔ circulating ILC2 outside allergen season in AR
Monocytes		• IL-1β • IL-6 • IL-10 • TNF-α	• pathogen defense • phagocytosis • antigen presentation • differentiation into macrophages or dendritic cells	• classical monocytes (CD14++CD16−) source for interstitial macrophages (?) • attracting effector cells • (↑) integrin adhesion molecule (CD11c) surface density in AR • monocyte-derived IL-10 downregulation by Th2 cytokines • (↑) circulating non-classical CD14++CD16+ and intermediate CD14 + CD16++ monocyte levels in AR • ↓ antigen presentation capacity after glucocorticoids • (↑) increased IL-10 production after AIT
Dendritic Cells	pDC mDC		• antigen presentation • activation of effector T cells • tolerance induction via activation of Tregs	• mucosal pDC and mDCs ↑ after allergen exposure in AR • mDCs have ↑ surface FcɛRI levels in AR • blood DCs express ↓ IL-10, IL-12 and IFN-α in AR (Th2 promotion?) • AIT ↑ DCs mediated naïve T-cells skewing towards IL-10-producing Tregs • AIT ↑ IFN-α production from pDCs • local corticosteroids disrupt allergen presentation of mucosal DCs
Eosinophils		• MBP • ECP • EPX • EDN	• helminth defense • allergic inflammation	• ↑ in nasal mucosa after allergen challenge • circulating eosinophils degranulate in target tissues • correlation with clinical symptoms eotaxin associated (?) • ↑ circulating eosinophil numbers in the late phase after allergen exposure in AR
Basophils		• histamine • serotonin • tryptase • PGD2 • LTC4 • PAF	• parasite defense • allergic inflammation	• enable IgE-dependent Th2 skewing after allergen contact • FcεRI1 expression • ↑ accumulation in nasal mucosa associated with clinical symptoms • (↓) circulating basophil numbers, but (↑) activation markers after allergen challenge in AR • (↓) responsiveness after AIT (IgG antibodies mediated basophil FcεRIIb blocking)
Neutrophils	Segmented neutrophil	• MMP-9 • elastase • α-defensin • TGF-ß1 • ROS	• first-line innate immune responses against pathogens • release of neutrophil extracellular traps (NETs) • phagocytosis	• supporting eosinophil migration and T cells priming • mediators associated with vasomotor symptoms • altered functions in LTB2 production, ROS generation and phagocytic activity in AR • ↑ circulating neutrophils in early phase after allergen challenge • ↓ nasal accumulation after montelukast therapy
Thrombocytes (Platelets)			• coagulation	• impaired aggregation correlating with IgE (?) • P-selectin mediated vascular attachment of leukocytes (?) • induction of DCs maturation and Th2 polarization (?)
Erythrocytes (RBCs)			• respiratory gas exchange	• ↓ circulating RBCs in early phase after allergen challenge in AR • neutrophil chemotaxis by DAMPs (heme, Hsp70 and IL-33) and ROS release (?)

↓ higher; ↑ lower; ↔ unchanged; (↑) inconsistent reports of higher numbers, (↓) inconsistent reports of lower numbers, (↨) reports of higher and lower numbers; AIT allergen immunotherapy, mDCs myeloid Dendritic Cells, pDCs plasmacytoid Dendritic Cells, ECP eosinophil cationic protein, EDN eosinophil-derived neurotoxin, EPX eosinophil peroxidase, LT leukotriene, NK Natural Killer Cell, ILC Innate Lymphoid Cell, MBP major basic protein, MMP matrix metalloprotease, RBC red blood cell, ROS reactive oxygen species; (?) suspected, or controversial studies ongoing