Regulatory ILC2-Role of IL-10 Producing ILC2 in Asthma

Over the past two decades, a growing body of evidence observations have shown group two innate lymphoid cells (ILC2) to be critical drivers of Type 2 (T2) inflammatory responses associated with allergic inflammatory conditions such as asthma. ILC2 releases copious amounts of pro-inflammatory T2 cytokines-interleukin (IL)-4, IL-5, IL-9, and IL-13. This review provides a comprehensive overview of the newly discovered regulatory subtype of ILC2 described in murine and human mucosal tissue and blood. These KLRG1+ILC2 have the capacity to produce the anti-inflammatory cytokine IL-10. Papers compiled in this review were based on queries of PubMed and Google Scholar for articles published from 2000 to 2023 using keywords IL-10 and ILC2. Studies with topical relevance to IL-10 production by ILC2 were included. ILC2 responds to microenvironmental cues, including retinoic acid (RA), IL-2, IL-4, IL-10, and IL-33, as well as neuropeptide mediators such as neuromedin-U (NMU), prompting a shift towards IL-10 and away from T2 cytokine production. In contrast, TGF-beta attenuates IL-10 production by ILC2. Immune regulation provided by IL-10+ILC2s holds potential significance for the management of T2 inflammatory conditions. The observation of context-specific cues that alter the phenotype of ILC warrants examining characteristics of ILC subsets to determine the extent of plasticity or whether the current classification of ILCs requires refinement.

Automated summary

Growing evidence suggests the critical role of ILC2 in allergic inflammatory conditions, and this review provides a comprehensive overview of a newly discovered regulatory subtype of ILC2. These ILC2 subsets, capable of producing the anti-inflammatory cytokine IL-10, hold potential significance for immune regulation and management of T2 inflammatory conditions.