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ILC2 cells, or type 2 innate lymphoid cells are a type of innate lymphoid cell. They are derived from common lymphoid progenitor and belong to the lymphoid lineage. These cells lack antigen specific B or T cell receptor because of the lack of recombination activating gene.[1] ILC2s produce type 2 cytokines (e.g. IL-4, IL-5, IL-9, IL-13).

The cell type were first described in 2001.[citation needed] In 2006, a similar cell population was identified in a case of helminthic infection.[citation needed] The name "ILC2" was not proposed until 2013.[2] They were previously identified in literature as natural helper cells[3], nuocytes, or innate helper 2 cells.[2]

Parasitic infection[edit]

ILC2s play the crucial role of secreting type 2 cytokines in response to helminth infection. They have also been implicated in the development of allergic lung inflammation.[4] They express characteristic surface markers and receptors for chemokines, which are involved in distribution of lymphoid cells to specific organ sites. They require IL-7 for their development, which activates two transcription factors (both required by these cells)—RORα and GATA3. After stimulation with Th2 polarising cytokines (e.g. IL-25, IL-33, TSLP) ILC2s start to produce IL-5, IL-13, IL-9, IL-4. ILC2s are critical for primary responses to local Th2 antigens e.g. helmints and viruses and that is why ILC2s are abundant in tissues of skin,[5] lungs, livers and gut.[6]

Allergy, atopic dermatitis, and asthma[edit]

ILC2s play a variety of roles in allergy.[4] Primarily, they provide a source of the type 2 cytokines that orchestrate the allergic immune response. They produce a profile of signals in response to pro-allergenic cytokines IL-25 and IL-33 that is similar to those produced in response to helminthic infection. Their contribution to this signaling appears to be comparable to that of T cells. In response to allergen exposure in the lungs, ILC2s produce IL-13, a necessary cytokine in the pathogenesis of allergic reactions. This response appears to be independent of T and B cells. Further, allergic responses that resemble asthma-like symptoms have been induced in mice that lack T and B cells using IL-33. It has also been found that ILC2s are present in higher concentrations in tissues where allergic symptoms are present, such as in the nasal polyps of patients with chronic rhinosinusitis and the skin from patients with atopic dermatitis.[7][8][9]


Research identified ILC2s in adipose tissue as a factor in the development of obesity in mice. ILC2s are critical in energy homeostasis by producing methionine-enkephalin peptides in response to IL-33. This production promotes the emergence of beige adipocytes in white adipose tissue. The process of beiging leads to increased energy expenditure and decreased adiposity.[10]


  1. ^ Spits H, Cupedo T (2012). "Innate lymphoid cells: emerging insights in development, lineage relationships, and function". Annual Review of Immunology. 30: 647–75. doi:10.1146/annurev-immunol-020711-075053. PMID 22224763.
  2. ^ a b Lund S, Walford HH, Doherty TA (November 2013). "Type 2 Innate Lymphoid Cells in Allergic Disease". Current Immunology Reviews. 9 (4): 214–221. doi:10.2174/1573395510666140304235916. PMC 4033554. PMID 24876829.
  3. ^ Moro, K; Yamada, T; Tanabe, M; Takeuchi, T; Ikawa, T; Kawamoto, H; Furusawa, J; Ohtani, M; Fujii, H; Koyasu, S (28 January 2010). "Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells". Nature. 463 (7280): 540–4. doi:10.1038/nature08636. PMID 20023630. Retrieved 27 January 2020.
  4. ^ a b Halim TY, Steer CA, Mathä L, Gold MJ, Martinez-Gonzalez I, McNagny KM, McKenzie AN, Takei F (March 2014). "Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation". Immunity. 40 (3): 425–35. doi:10.1016/j.immuni.2014.01.011. PMC 4210641. PMID 24613091.
  5. ^ Roediger B, Kyle R, Yip KH, Sumaria N, Guy TV, Kim BS, Mitchell AJ, Tay SS, Jain R, Forbes-Blom E, Chen X, Tong PL, Bolton HA, Artis D, Paul WE, Fazekas de St Groth B, Grimbaldeston MA, Le Gros G, Weninger W (June 2013). "Cutaneous immunosurveillance and regulation of inflammation by group 2 innate lymphoid cells". Nature Immunology. 14 (6): 564–73. doi:10.1038/ni.2584. PMC 4282745. PMID 23603794.
  6. ^ Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, Langford TK, Bucks C, Kane CM, Fallon PG, Pannell R, Jolin HE, McKenzie AN (April 2010). "Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity". Nature. 464 (7293): 1367–70. doi:10.1038/nature08900. PMC 2862165. PMID 20200518.
  7. ^ Kim, Brian; et al. (2013). "TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation". Science Translational Medicine. 5 (170). doi:10.1126/scitranslmed.3005374. PMC 3637661. PMID 23363980.
  8. ^ Oboki K, Nakae S, Matsumoto K, Saito H (April 2011). "IL-33 and Airway Inflammation". Allergy, Asthma & Immunology Research. 3 (2): 81–8. doi:10.4168/aair.2011.3.2.81. PMC 3062800. PMID 21461246.
  9. ^ Kondo H, Ichikawa Y, Imokawa G (March 1998). "Percutaneous sensitization with allergens through barrier-disrupted skin elicits a Th2-dominant cytokine response". European Journal of Immunology. 28 (3): 769–79. doi:10.1002/(SICI)1521-4141(199803)28:03<769::AID-IMMU769>3.0.CO;2-H. PMID 9541570.
  10. ^ Brestoff JR, Kim BS, Saenz SA, Stine RR, Monticelli LA, Sonnenberg GF, Thome JJ, Farber DL, Lutfy K, Seale P, Artis D (March 2015). "Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity". Nature. 519 (7542): 242–6. doi:10.1038/nature14115. PMC 4447235. PMID 25533952.