A stromal cell niche sustains ILC2-mediated type-2 conditioning in adipose tissue

Author:

Rana Batika M.J.1,Jou Eric1,Barlow Jillian L.1,Rodriguez-Rodriguez Noe1,Walker Jennifer A.1,Knox Claire1,Jolin Helen E.1,Hardman Clare S.1,Sivasubramaniam Meera1,Szeto Aydan1,Cohen E. Suzanne2ORCID,Scott Ian C.2ORCID,Sleeman Matthew A.2,Chidomere Chiamaka I.3,Cruz Migoni Sara3,Caamano Jorge3ORCID,Jorgensen Helle F.4ORCID,Carobbio Stefania56,Vidal-Puig Antonio56,McKenzie Andrew N.J.1ORCID

Affiliation:

1. Medical Research Council Laboratory of Molecular Biology, Cambridge, UK

2. Department of Respiratory, Inflammation and Autoimmunity, AstraZeneca, Cambridge, UK

3. College of Medical and Dental Sciences, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

4. Cardiovascular Medicine Division, Department of Medicine, University of Cambridge, Cambridge, UK

5. Wellcome Trust Sanger Institute, Hinxton, UK

6. Metabolic Research Laboratories, Addenbrooke's Treatment Centre, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK

Abstract

Group-2 innate lymphoid cells (ILC2), type-2 cytokines, and eosinophils have all been implicated in sustaining adipose tissue homeostasis. However, the interplay between the stroma and adipose-resident immune cells is less well understood. We identify that white adipose tissue–resident multipotent stromal cells (WAT-MSCs) can act as a reservoir for IL-33, especially after cell stress, but also provide additional signals for sustaining ILC2. Indeed, we demonstrate that WAT-MSCs also support ICAM-1–mediated proliferation and activation of LFA-1–expressing ILC2s. Consequently, ILC2-derived IL-4 and IL-13 feed back to induce eotaxin secretion from WAT-MSCs, supporting eosinophil recruitment. Thus, MSCs provide a niche for multifaceted dialogue with ILC2 to sustain a type-2 immune environment in WAT.

Funder

Medical Research Council

Wellcome Trust

MedImmune

AstraZeneca

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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