Thymic Epithelial Cell-Derived IL-15 and IL-15 Receptor α Chain Foster Local Environment for Type 1 Innate Like T Cell Development

Front Immunol. 2021 Mar 1;12:623280. doi: 10.3389/fimmu.2021.623280. eCollection 2021.

Abstract

Expression of tissue-restricted antigens (TRAs) in thymic epithelial cells (TECs) ensures negative selection of highly self-reactive T cells to establish central tolerance. Whether some of these TRAs could exert their canonical biological functions to shape thymic environment to regulate T cell development is unclear. Analyses of publicly available databases have revealed expression of transcripts at various levels of many cytokines and cytokine receptors such as IL-15, IL-15Rα, IL-13, and IL-23a in both human and mouse TECs. Ablation of either IL-15 or IL-15Rα in TECs selectively impairs type 1 innate like T cell, such as iNKT1 and γδT1 cell, development in the thymus, indicating that TECs not only serve as an important source of IL-15 but also trans-present IL-15 to ensure type 1 innate like T cell development. Because type 1 innate like T cells are proinflammatory, our data suggest the possibility that TEC may intrinsically control thymic inflammatory innate like T cells to influence thymic environment.

Keywords: IL-15; IL-15Rα; iNKT cells; thymic epithelial cells; type 1 innate like T cells; γδT cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication
  • Cellular Microenvironment
  • Databases, Genetic
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism*
  • Humans
  • Immunity, Innate*
  • Interleukin-15 / genetics
  • Interleukin-15 / metabolism*
  • Intraepithelial Lymphocytes / immunology
  • Intraepithelial Lymphocytes / metabolism
  • Mice
  • Mice, Knockout
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism
  • Receptors, Interleukin-15 / genetics
  • Receptors, Interleukin-15 / metabolism*
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • Thymocytes / immunology
  • Thymocytes / metabolism*
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Thymus Gland / metabolism*

Substances

  • IL15 protein, human
  • IL15RA protein, human
  • Il15ra protein, mouse
  • Interleukin-15
  • Receptors, Interleukin-15