Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria

Hepworth, Matthew R.; Monticelli, Laurel A.; Fung, Thomas C.; Ziegler, Carly G. K.; Grunberg, Stephanie; Sinha, Rohini; Mantegazza, Adriana R.; Ling, Hak; Crawford, Alison; Angelosanto, Jill; Wherry, E. John; Koni, Pandelakis A.; Bushman, Frederic D.; Elson, Charles O.; Eberl, Gérard; Artis, David; Sonnenberg, Gregory F.

doi:10.1038/nature12240

Cited by 665 publications

(743 citation statements)

References 32 publications

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“…Recent data suggested that ILC3 also may modulate T cell responses in the gut (23). This effect also appeared to involve an MHC class II-dependent mechanism; however, and in contrast to the data reported in this article, ILC3 appeared to limit, rather than promote, Th17 cell activation (24).…”

Section: Discussioncontrasting

confidence: 81%

Type 2 Innate Lymphoid Cells Drive CD4+ Th2 Cell Responses

Mirchandani

Besnard

Yip

et al. 2014

The Journal of Immunology

276

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CD4+ T cells have long been grouped into distinct helper subsets on the basis of their cytokine-secretion profile. In recent years, several subsets of innate lymphoid cell have been described as key producers of these same Th-associated cytokines. However, the functional relationship between Th cells and innate lymphoid cells (ILCs) remains unclear. We show in this study that lineage-negative ST2+ICOS+CD45+ type 2 ILCs and CD4+ T cells can potently stimulate each other’s function via distinct mechanisms. CD4+ T cell provision of IL-2 stimulates type 2 cytokine production by type 2 ILCs. By contrast, type 2 ILCs modulate naive T cell activation in a cell contact–dependent manner, favoring Th2 while suppressing Th1 differentiation. Furthermore, a proportion of type 2 ILCs express MHC class II and can present peptide Ag in vitro. Importantly, cotransfer experiments show that type 2 ILCs also can boost CD4+ T cell responses to Ag in vivo.

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Section: Discussioncontrasting

confidence: 81%

Type 2 Innate Lymphoid Cells Drive CD4+ Th2 Cell Responses

Mirchandani

Besnard

Yip

et al. 2014

The Journal of Immunology

276

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“…In the intestine, RORγt + CCR6 + ILC3s expressing MHC‐II control intestinal homeostasis through cognate interactions with CD4 + T cells 3, 8, 9. In the adult spleen, RORγt + CCR6 + ILC3s promote CD4 + T‐cell responses and enhance antibody production by marginal zone B cells 4, 28.…”

Section: Resultsmentioning

confidence: 99%

“…Splenic ILC3s were enriched by using lineage cell depletion kit (Miltenyi Biotec). ILC3s were further purified by cell sorting as CD45 + CD127 + CD117 + B220 − CD3 − CD5 − CD11c − CD11b − cells 3, 9, 28 with a FACSAria II (BD Biosciences). Sorted ILC3s were cultured in complete RPMI medium supplemented with 10% FCS.…”

Section: Methodsmentioning

confidence: 99%

CD 1d‐mediated activation of group 3 innate lymphoid cells drives IL ‐22 production

et al. 2016

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Innate lymphoid cells (ILCs) are a heterogeneous family of immune cells that play a critical role in a variety of immune processes including host defence against infection, wound healing and tissue repair. Whether these cells are involved in lipid‐dependent immunity remains unexplored. Here we show that murine ILCs from a variety of tissues express the lipid‐presenting molecule CD1d, with group 3 ILCs (ILC3s) showing the highest level of expression. Within the ILC3 family, natural cytotoxicity triggering receptor (NCR)− CCR6+ cells displayed the highest levels of CD1d. Expression of CD1d on ILCs is functionally relevant as ILC3s can acquire lipids in vitro and in vivo and load lipids on CD1d to mediate presentation to the T‐cell receptor of invariant natural killer T (iNKT) cells. Conversely, engagement of CD1d in vitro and administration of lipid antigen in vivo induce ILC3 activation and production of IL‐22. Taken together, our data expose a previously unappreciated role for ILCs in CD1d‐mediated immunity, which can modulate tissue homeostasis and inflammatory responses.

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“…susceptibles à la colite ayant pour origine l'activation des lymphocytes T [44]. Enfin, les LTi, qui font partie des ILC de type 3, sont essentielles à la formation des tissus lymphoïdes au cours de l'embryogenèse [1].…”

Section: Tableau I (Suite)unclassified