Activated group 3 innate lymphoid cells promote T-cell-mediated immune responses

Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12835-40. doi: 10.1073/pnas.1406908111. Epub 2014 Aug 18.

Abstract

Group 3 innate lymphoid cells (ILC3s) have emerged as important cellular players in tissue repair and innate immunity. Whether these cells meaningfully regulate adaptive immune responses upon activation has yet to be explored. Here we show that upon IL-1β stimulation, peripheral ILC3s become activated, secrete cytokines, up-regulate surface MHC class II molecules, and express costimulatory molecules. ILC3s can take up latex beads, process protein antigen, and consequently prime CD4(+) T-cell responses in vitro. The cognate interaction of ILC3s and CD4(+) T cells leads to T-cell proliferation both in vitro and in vivo, whereas its disruption impairs specific T-cell and T-dependent B-cell responses in vivo. In addition, the ILC3-CD4(+) T-cell interaction is bidirectional and leads to the activation of ILC3s. Taken together, our data reveal a novel activation-dependent function of peripheral ILC3s in eliciting cognate CD4(+) T-cell immune responses.

Keywords: T-cell activation; antigen presentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism
  • Histocompatibility Antigens Class II / immunology
  • Immunity, Cellular / immunology
  • Interleukin-1beta / immunology*
  • Interleukin-1beta / pharmacology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology*
  • Lymphocytes / drug effects
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction / immunology*

Substances

  • Cytokines
  • Histocompatibility Antigens Class II
  • Interleukin-1beta