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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