Invariant NKT Cells Require Autophagy to Coordinate Proliferation and Survival Signals During Differentiation

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2015 May 1

PMID 25926673

Citations 48

Authors

Bo Pei

Meng Zhao

Brian C Miller

Jose Luis Vela

Monique W Bruinsma

Herbert W Virgin

Mitchell Kronenberg

Affiliations

Soon will be listed here.

Abstract

Autophagy regulates cell differentiation, proliferation, and survival in multiple cell types, including cells of the immune system. In this study, we examined the effects of a disruption of autophagy on the differentiation of invariant NKT (iNKT) cells. Using mice with a T lymphocyte-specific deletion of Atg5 or Atg7, two members of the macroautophagic pathway, we observed a profound decrease in the iNKT cell population. The deficit is cell-autonomous, and it acts predominantly to reduce the number of mature cells, as well as the function of peripheral iNKT cells. In the absence of autophagy, there is reduced progression of iNKT cells in the thymus through the cell cycle, as well as increased apoptosis of these cells. Importantly, the reduction in Th1-biased iNKT cells is most pronounced, leading to a selective reduction in iNKT cell-derived IFN-γ. Our findings highlight the unique metabolic and genetic requirements for the differentiation of iNKT cells.

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