Type 2 Innate Lymphoid Cells: Friends or Foes—Role in Airway Allergic Inflammation and Asthma

Table 1

Innate-like lymphocytes (ILLs) family.

Cell type

Date of discovery; and naming in the first publish

Main development; location

Major transcription; factors and molecules; needed for development

Anatomical locations

Developmental stage; that derived from; common progenitor

Major cytokines; produced by cells

Major stimulating; cytokines

Activator; and proliferator cells

Antigen; receptor

Ligands

Major; surface markers

MHC/MHC-like restriction

Major functions and pathology

Antimicrobial defense mechanisms

Reference

MAIT

(i) Porcelli et al. 1993 [3]; (ii) Tilloy et al. 1999 [4]

Thymus

PLZF (ZBTB16) in human

(i) Gut lamina propria; (ii) Liver (human); (iii) Blood (few numbers)

Late double negative (DN)

IL-4; IL-5; IL-10; IL-17; IFN-𝛾; TNF-𝛼

IL-1𝛽

(i) B cells; (ii) Gut normal flora

TCR 𝛼/𝛽; V𝛼19 (mouse); V𝛼7.2 (human)

Hydrophobic molecules

IL-12R, IL-18R, IL-23R; CD4^−CD8^−, CD8𝛼^+ (human), CD161 (NKR-P1A), NKG2D, NKP30, P80, CCR6, CXCR6

MR1 (class Ib) restriction

(i) Possible regulation of inflammation in autoimmune disorders; (ii) Regulation of IgA production in gut; (iii) Intestinal homeostasis; (iv) CNS pathology

(i) Cytokine production; (ii) Cellular recruitment and recalling; (iii) Cytotoxicity (Fas, granzymes)

[3–6]

iNKT

(i) In mouse: Koseki et al. 1990 [7]; (ii) In human: Porcelli; et al. 1993 [3]

Thymus

PLZF; SLAM

Peripheral lymph tissues such as liver, spleen, and lymph nodes

Double positive (DP) (pro-T)

IL-4; IL-10; IL-13; IFN-𝛾; TGF-𝛽

IL-7; IL-12; IL-25; IL-33; TSLP

APCs

TCR 𝛼/𝛽; V𝛼14 (mouse); V𝛼24 (human)

Glycolipids especially 𝛼-Gal-Cer

DN or CD4^+ (mouse),; DN or CD8^+ or CD4^+ (human), CD28, ICOS, NK1.1, NKG2D

CD1d

(i) Immune regulation; (ii) Immunity against infection; (iii) Graft rejection and GVHD; (iv) Pathogenesis of cancers, allergy, and autoimmune disorders

(i) Cytokine storm in a few minutes to hours; (ii) Cellular recruitment and recalling

[3, 7–10]

𝛾/𝛿 T cell

(i) Saito et al. 1984 [11]; (ii) Samelson et al. 1985 [12]

Thymus

Sox13; Id3; Egr-1

(i) Epiderm; (ii) Mucosal tissues; (iii) Blood (few numbers)

DN2

IL-17; IFN-𝛾; TNF-𝛼

IL-2; IL-7; IL-21

(i) Mostly by antigens directly; (ii) APCs (less common)

TCR; 𝛾/𝛿

Mostly nonpeptidic-self and nonself-antigens

NKRs: KIRs and NKG2A, C, D, TLRs, CCR7, CD16, CD226, MHC II, cytokine receptors

(i) Mostly no need to MHC restriction (direct recognition); (ii) MHC/MHC-like restriction (less common)

(i) Immune regulation; (ii) Immunity against infection; (iii) Tissue repair

(i) Cytokine production; (ii) Cellular recruitment and recalling; (iii) Cytotoxicity (Fas, granzymes, perforin)

[11–16]

MZB

MacLennan et al. 1982; [17]

Spleen marginal zone

BAFF; Pyk-2; Notch2

(i) Spleen; (ii) Blood (few numbers); (iii) Few numbers in Peyer’s patches and lymph node subcapsular sinus

T1/T2 (immature B cell)

IL-6; IL-10; IFN-β

IL-7; IL-21

(i) APCs; (ii) Mostly T independent; (iii) Directly by antigen; (iv) T dependent (less common)

BCR: IgM^hi; IgD^low

Mostly nonpeptidic antigens

CD1, CD9, CD27, CD36, CD11b, GP49b, TLRs, S1P1, MHC II, FC-like receptors,; CD23^−

CD1; (less common)

(i) Immunity against blood-borne infections; (ii) Immunity against encapsulate bacteria; (iii) Response to autoantigens derived from senescence

IgM and IgG3 production

[17–20]

B1-B cell

(i) Gronowicz and Coutinho 1975 [21]; (ii) Hayakawa et al. 1983 [22]

Firstly in BM, then located in; tissue

BAFF; NFATc1; Siglec-G

(i) Peritoneal and pleural cavity; (ii) Lungs; (iii) Blood (few numbers)

T1/T2 (immature B cell)

IL-6; IL-10; TNF-𝛼

IL-5

(i) Mostly T independent; (ii) Directly by antigens

BCR: IgM^hi; IgD^low

Mostly nonpeptidic-self and nonself-antigens

CD1, CD5, CD19, CD20, CD22, CD27, CD9, CD11b, CD43, B220

CD1; (less common)

(i) Natural antibody production; (ii) Immunity against infection; (iii) Pathogenesis of autoimmune disorders and CLL

(i) IgM production; (ii) IgG3 production (less common); (iii) IgA production in gut

[21–28]

MAIT: mucosal-associated invariant T cells, iNKT: invariant natural killer T cells, MZB: marginal zone B cells, MR1: MHC-related protein-1, Egr: early growth response, Id3: inhibitor of DNA binding-3, BAFF: B cell activation factor of the TNF family, Pyk: protein tyrosine kinase, Notch2: neurogenic locus notch homology protein 2, NFATc1: nuclear factor of activated T cell, cytoplasmic-1, S1P1: sphingosine-1-phosphate receptor-1, Sox: sex-determining region-(sry-) related high-mobility-group (HMG) box, PLZF: promyelocytic leukemia zinc finger, α-Gal-Cer: alpha-galactosylceramide, SLAM: signaling lymphocytic activation molecule, CLL: chronic lymphocytic leukemia.