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Table 1 Circulating blood cells involved in AR-associated inflammation

From: The impact of allergen exposure and specific immunotherapy on circulating blood cells in allergic rhinitis

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 (?)
  1. ↓ 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