Notch Signaling Regulates the Homeostasis of Tissue-Restricted Innate-like T Cells.

Chennupati V; Koch U; Coutaz M; Scarpellino L; Tacchini-Cottier F; Luther SA; Radtke F; Zehn D; MacDonald HR

doi:10.4049/jimmunol.1501675

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Journal article

Notch Signaling Regulates the Homeostasis of Tissue-Restricted Innate-like T Cells.

Chennupati V Ludwig Centre for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland; Swiss Vaccine Research Institute, Lausanne University Hospital, 1066 Epalinges, Switzerland; Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, 1066 Epalinges, Switzerland; hughrobson.macdonald@unil.ch vijaykumar.chennupati@unil.ch.
Koch U Swiss Federal Institute of Technology Lausanne, School of Life Sciences, Swiss Institute for Experimental Cancer Research, 1015 Lausanne, Switzerland;
Coutaz M Department of Biochemistry, World Health Organization Immunology Research and Training Centre, University of Lausanne, 1066 Epalinges, Switzerland; and.
Scarpellino L Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
Tacchini-Cottier F Department of Biochemistry, World Health Organization Immunology Research and Training Centre, University of Lausanne, 1066 Epalinges, Switzerland; and.
Luther SA Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
Radtke F Swiss Federal Institute of Technology Lausanne, School of Life Sciences, Swiss Institute for Experimental Cancer Research, 1015 Lausanne, Switzerland;
Zehn D Swiss Vaccine Research Institute, Lausanne University Hospital, 1066 Epalinges, Switzerland; Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, 1066 Epalinges, Switzerland;
MacDonald HR Ludwig Centre for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland; hughrobson.macdonald@unil.ch vijaykumar.chennupati@unil.ch.

2016-06-22

Published in:

Journal of immunology (Baltimore, Md. : 1950). - 2016

English Although Notch signaling plays important roles in lineage commitment and differentiation of multiple cell types including conventional T cells, nothing is currently known concerning Notch function in innate-like T cells. We have found that the homeostasis of several well-characterized populations of innate-like T cells including invariant NKT cells (iNKT), CD8ααTCRαβ small intestinal intraepithelial lymphocytes, and innate memory phenotype CD8 T cells is controlled by Notch. Notch selectively regulates hepatic iNKT cell survival via tissue-restricted control of B cell lymphoma 2 and IL-7Rα expression. More generally, Notch regulation of innate-like T cell homeostasis involves both cell-intrinsic and -extrinsic mechanisms and relies upon context-dependent interactions with Notch ligand-expressing fibroblastic stromal cells. Collectively, using conditional ablation of Notch receptors on peripheral T cells or Notch ligands on putative fibroblastic stromal cells, we show that Notch signaling is indispensable for the homeostasis of three tissue-restricted populations of innate-like T cells: hepatic iNKT, CD8ααTCRαβ small intestinal intraepithelial lymphocytes, and innate memory phenotype CD8 T cells, thus supporting a generalized role for Notch in innate T cell homeostasis.

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