screen-shot-2017-02-22-at-10-03-47-pmILCs exist in 3 main flavors: ILC1, ILC2, and ILC3s. Unique subsets of ILC1 and ILC3s have been identified; however, it has been unclear as to whether phenotypic or functionally different subsets of ILC2s exist.

figure-1-human-ilc-subsets-closely-resemble-t-cell-lineages-within-the-ncr-ilc-subset

Nature Reviews Gastroenterology &#38 Hepatology 12(5):271-283 · May 2015

ILC2s, which modulate helminth immunity and asthma, are responsive to many cytokines, including IL-33 and IL-25. This study by Huang et al. demonstrates that the ILC2s that respond to IL-33 or IL-25 are phenotypically different.

In response to IL-33, there is a modest increase in ST2-expressing ILCs (natural ILCs), whereas in response to IL-25 there is a dramatic expansion of KLRG1+ ILCs (“inflammatory” ILCs).

 

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Further, the natural and “inflammatory” ILC2s exhibit differential expression of other molecules such as IL-7Rα, IL-17RB, CD44, and Sca-1.

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Development of iILC2s (“inflammatory”) is dependent on ϒc and IL-7Rα. Additionally,  iILC2s express more IL-13 compared to nILCs (natural) in response to IL25.

During N. brasiliensis (helminth) infection, iILCs appeared in the lung earlier than nILCs. Transfer of either ILC subset into a newly infected host demonstrated that both ILC were equally capable of  cleaning worms.  Additionally, iILCs became nILCs in vivo, thus suggesting that nILCs were progenitors for nILCs.

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Additionally, iILC express more GATA-3 than nILCs, and iILCs also express RORϒt and limit oral fungal infections in mice.

 

Thus, KLRG1+ “inflammatory” ILCs represent a distinct subset of ILC2 from the homeostatic ST2+ natural ILCs. Additionally, iILCs give rise to natural ILCs in vitro and in vivo, and it does not appear that nILCs give rise to iILCs.

It is not clear to me what makes the KLRG1+ iILC population inflammatory, since these cells are equally able to expel helminth compared to nILCs. Additionally, the developmental origin of these cells has not yet been identified.

 

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