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

Table 3

Type2 innatel cells (ILCs2) populations.

Name	Date of discovery; and naming in the first publish	Species	Tissue; distribution	Cytokines; produced; by cells	Stimulating; and; development; -effective; cytokines	Transcription; factors and; molecules; needed for; development	Surface phenotype	Functions and pathology	Reference
Natural helper; cells (NHCs)	(i) Fort et al. 2001 [40]; (ii) Hurst et al. 2002 [41]; (iii) Moro et al. 2010 [42]	Wild-type; mouse	FALT; Lung	*(i) IL-5, IL-13; (ii) IL-4, IL-6, IL-2; IFN-𝛾	*(i) IL-25, IL-33; (ii) IL-2/IL-25; (iii) SCF/IL-7; (iv) TSLP	*Id2, GATA-3,; Stat-6, c-Maf,; Jun-b, T-bet^low,; ETS-1	Lin^−, c-kit (CD117), Sca1 (ly6a),; IL-7Rα (CD127), CD44,; IL-2Rα (CD25), ST2 (IL-33R),; CD45, CD69, CD90.2 (Thy1.2), Flt3	(i) Nematode expulsion; (ii) Induction of airway pathology following viral infection; (iii) Tissue repair following influenza virus infection; (iv) B1-B cell renewal; (v) IgA production by splenic B cells; (vi) Goblet cell hyperplasia	[40–49]
Nuocytes	(i) Neill et al. 2010 [50]	IL-13-GFP; reporter mouse	Intestine; mLN; Spleen	*(i) IL-5, IL-13; (ii) IL-4, IL-6, IL-10; (iii) IL-2, GM-CSF; (iv) CCL3 (MIP1𝛼)	*(i) IL-25, IL-33; (ii) IL-7	*Id2,; Notch-1, RoR-𝛼,; GATA-3, c-Maf,; Stat-6, Jun-b	Lin^−, c-kit^+/−, CD44, MHC II, Sca1,; IL-12RB, IL-7Rα ^+/low, IL-17RA,; ICOS (CD278), Klrg1, ST2^+/−,; IL-10RB, IL-17RB (IL-25R), CD45,; CD90.2, IL-27R (wsx1),; ICAM-1, ICAM-2, CCR9, CXCR4,; CXCR6, B7 integrin	(i) Nematode expulsion; (ii) Increase in goblet cell mucin; (iii) Increase in T-cell response	[43–45, 50–52]
Innate helper2; (Ih2) cells	(i) Price et al. 2010 [53]	IL-13-GFP; and; IL-4-GFP; reporter mouse	Broad, mostly in lung, spleen, mLN, and liver	*(i) IL-5, IL-13; (ii) IL-4	*(i) IL-25, IL-33	*Id2,; GATA-3,; Stat-6, aiolos	Lin^−, c-kit^+/−/low, Sca1^−, CD45,; IL-2Rα, CD90.2, CD44, ST2, CD69	(i) Nematode expulsion; (ii) Increase in eosinophils	[43, 44, 52–54]
Type2 innate; lymphoid cells; (ILCs2)	(i) Mjösberg et al. 2011 [55]	Human	(i) Fetal/adult gut and lung; (ii) Palatin tonsils; (iii) Nasal polyps; (iv) Adult; peripheral blood	*(i) IL-5, IL-13	*(i) IL-25/IL-2; *(ii) IL-33/IL-2	*Id2,; ETS-1, GATA-3	Lin^−, c-kit^+/−, IL-7Rα, IL-2Rα,; ST2, IL-17RB, CD45,; CRTH2 (GPR44, CD294); CD161 (NKR-P1A)	(i) Chronic rhinosinusitis	[47, 55]
Multipotent; progenitor; population 2; (MPP^type2)	Saenz et al. 2010 [56]	IL-4-GFP; reporter mouse	(i) mLN; (ii) GALT especially in; Peyer’s patches; and cecal patch	*(i) IL-5, IL-13; (mostly mRNA); (ii) IL-4; (mostly mRNA)	*(i) IL-25; (ii) SCF; (iii) IL-3	*Id2,; c-Maf^−/low,; GATA-3^−/low; Stat-6^−/low	Lin^−, c-kit, Sca1, CD45,; ST2^−/low, IL-17RB, CD34^−/low,; IL-7Rα ^−/low, CD62L^−/low,; **MHC II	(i) Nematode expulsion; (ii) Increase in goblet cell mucin; (iii) Increase in T-cell response	[43–45, 52, 56]

* The most important
** GFP⁻ cells expressed MHC II after cultivation with a combination of IL-3/SCF.
FALT: fat-associated lymphoid tissue, mLN: mesenteric lymph nodes, GFP: green fluorescent protein, GALT: gut-associated lymphatic tissues, Icos: inducible costimulatory molecule, CRTH2: chemoattractant receptor-homologous molecule expressed on Th2 lymphocytes, SCF: stem cell factor, GPR44: G protein-coupled receptor 44, ETS: E-twenty-six family, Flt3: Fms-related tyrosine kinase3.