S1P-dependent interorgan trafficking of group 2 innate lymphoid cells supports host defense

Science. 2018 Jan 5;359(6371):114-119. doi: 10.1126/science.aam5809.

Abstract

Innate lymphoid cells (ILCs) are innate counterparts of adaptive T lymphocytes, contributing to host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. ILCs have been considered to be tissue-resident cells, but whether ILCs move between tissue sites during infection has been unclear. We show here that interleukin-25- or helminth-induced inflammatory ILC2s are circulating cells that arise from resting ILC2s residing in intestinal lamina propria. They migrate to diverse tissues based on sphingosine 1-phosphate (S1P)-mediated chemotaxis that promotes lymphatic entry, blood circulation, and accumulation in peripheral sites, including the lung, where they contribute to anti-helminth defense and tissue repair. This ILC2 expansion and migration is a behavioral parallel to the antigen-driven proliferation and migration of adaptive lymphocytes to effector sites and indicates that ILCs complement adaptive immunity by providing both local and distant tissue protection during infection.

Publication types

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

MeSH terms

  • Adaptive Immunity
  • Animals
  • Cell Proliferation
  • Chemotaxis / immunology*
  • Female
  • Fingolimod Hydrochloride / pharmacology
  • Homeodomain Proteins / genetics
  • Homeostasis
  • Immunity, Innate*
  • Immunosuppressive Agents / pharmacology
  • Interleukin-17 / immunology*
  • Intestines / immunology
  • Lung / immunology
  • Lymphocytes / immunology*
  • Lysophospholipids / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mucous Membrane / immunology
  • Nippostrongylus / immunology*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / immunology
  • Strongylida Infections / immunology*
  • T-Lymphocytes / immunology

Substances

  • Homeodomain Proteins
  • Immunosuppressive Agents
  • Interleukin-17
  • Lysophospholipids
  • RAG-1 protein
  • sphingosine 1-phosphate
  • Fingolimod Hydrochloride
  • Sphingosine