CD1d-mediated activation of group 3 innate lymphoid cells drives IL-22 production.

Julia Saez De Guinoa,Peter J Jervis,Liam R Cox,Patricia Barral,Nazanin Farhadi,Gurdyal S Besra,Rebeca Jimeno

doi:10.15252/embr.201642412

Julia Saez De Guinoa, Peter J Jervis + Show 5 more

Open Access

https://doi.org/10.15252/embr.201642412

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Journal: EMBO reports	Publication Date: Oct 31, 2016
Citations: 39	License type: CC BY 4.0

Affiliation: University of Birmingham, King's College London

Abstract

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.

Highlights

Innate lymphoid cells (ILCs) are a family of immune cells that play a central role in a variety of physiological processes including immune regulation, modulation of interactions with the microbiota, tissue repair and lymphoid tissue development [1]
ILCs can be classified in three families based on their cytokine secretion and the transcription factors required for their development: ILC1s (T-bet+) produce IFN-c; ILC2s (GATA-3+) secrete IL-5 and IL-13; and ILC3s (RORct+) produce IL-17 and IL-22 [2]
To investigate the expression of the lipid-presenting molecule CD1d by ILCs, we first identified them as lineage (Lin)ÀCD45+CD127+ cells and used the expression of T-bet, GATA-3 and RORct to discriminate the ILC1, ILC2 and ILC3 populations, respectively (Figs 1 and EV1)

Summary

Introduction

Innate lymphoid cells (ILCs) are a family of immune cells that play a central role in a variety of physiological processes including immune regulation, modulation of interactions with the microbiota, tissue repair and lymphoid tissue development [1]. 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. We investigated the capacity of ILCs to internalize and load lipids on CD1d for presentation to the TCR of iNKT cells (Fig 2).

Results

Conclusion