Beyond Unconventional: What Do We Really Know about Group 2 Innate Lymphoid Cells?

Abstract

Group 2 innate lymphoid cells (ILC2s) are a set of effectors that mediate the expulsion of helminthic parasites but also drive allergic lung inflammation. As innate agents, they do not recognize Ag, instead, they are sensitive to alarmin engagement, upon which they produce type 2 cytokines that amplify adaptive immunity. Their lymphoid identity appoints them as an intriguing group of unconventional cells; however, increasing evidence is unraveling a series of unprecedented functions that <5 years ago were unthinkable for ILC2s, such as acquiring a proinflammatory identity that enables them to support TH1 immune responses. Their plastic nature has allowed the characterization of ILC2s in more detail than ever; however, the novelty of ILC2 biology requires constant updates and recapitulations. This review provides an overview of ILC2s and describes memory ILC2, regulatory ILC2, inflammatory ILC2, and type 1 ILC2 subsets based on activation status, tissue environments, and function.

A diversity of novel type-2 innate lymphoid cell subpopulations revealed during tumour expansion

“…Therefore, reduced IL-33 expression in metastatic mouse carcinomas simultaneously decreases both the MHC-I expression and the functional activities of ILC2s and provides a previously undescribed mechanism of immune escape for tumour cells. Moreover, we demonstrated a similar association between IL-33 and HLA expression in clinical specimens at different stages of human prostate tumour development 20 – 22 . Our work also documented that the presence of ILC2s significantly inhibits tumour formation in wild-type chimeric mice bearing tumours expressing IL-33 when compared to RORα -/- chimeras, which lack ILC2s.…”

“…Next, we assigned cluster identities by their over-represented hallmark pathways and expression profiles of selected genes-of-interest (GOI), inferring some of the important anti-tumoral immune functions (Table 1 ). The selected GOI are markers canonically known to be involved in different proposed ILC2 subpopulations 22 and mechanisms of immune functions such as Th1, Th2, T cell recruitment, antigen-presentation pathways (APP). The expression levels of GOI vary across each of the clusters (Fig.…”

Intratumor Childhood Vaccine-Specific CD4+T cell Recall Coordinates Antitumor CD8+T cells and Eosinophils

“…The copyright holder for this preprint this version posted March 14, 2022. ; https://doi.org/10.1101/2022.03.14.484260 doi: bioRxiv preprint been observed 45 , including their transition to a "Th1-like" state 46,47 . Perhaps highlighting the importance of context, both eosinophils and ILC2s have also been shown to mediate protumorigenic effects [48][49][50] .…”

“…Indeed, despite stagnant or even reduced expression of PD1 on T cells after recall antigen treatment, recall antigen therapy accentuated the antitumor efficacy of PD1 blockade. Varying ILC2 phenotype states have been observed 45 , including their transition to a "Th1-like" state 46,47 . Perhaps highlighting the importance of context, both eosinophils and ILC2s have also been shown to mediate protumorigenic effects [48][49][50] .…”

Functional Recognition Theory and Type 2 Immunity: Insights and Uncertainties

“…For instance, ILC2s can be trained by previous inflammation to acquire memory-like properties (102,103). On activation, ILC2s proliferate in situ and produce type 2 cytokines to induce inflammation (104). While the ILC2 population subsequently contracts, the number of memory-like ILC2s remains greater than the naive state (102,105).…”