Invariant NKT cells require autophagy to coordinate proliferation and survival signals during differentiation

Bo Pei, Meng Zhao, Brian C. Miller, Jose Luis Véla, Monique W. Bruinsma, Herbert W. Virgin, Mitchell Kronenberg

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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.

Original languageEnglish
Pages (from-to)5872-5884
Number of pages13
JournalJournal of Immunology
Volume194
Issue number12
DOIs
StatePublished - Jun 15 2015

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