Spatial distribution of LTi-like cells in intestinal mucosa regulates type 3 innate immunity

Proc Natl Acad Sci U S A. 2021 Jun 8;118(23):e2101668118. doi: 10.1073/pnas.2101668118.

Abstract

Lymphoid tissue inducer (LTi)-like cells are tissue resident innate lymphocytes that rapidly secrete cytokines that promote gut epithelial integrity and protect against extracellular bacterial infections.Here, we report that the retention of LTi-like cells in conventional solitary intestinal lymphoid tissue (SILT) is essential for controlling LTi-like cell function and is maintained by expression of the chemokine receptor CXCR5. Deletion of Cxcr5 functionally unleashed LTi-like cells in a cell intrinsic manner, leading to uncontrolled IL-17 and IL-22 production. The elevated production of IL-22 in Cxcr5-deficient mice improved gut barrier integrity and protected mice during infection with the opportunistic pathogen Clostridium difficile Interestingly, Cxcr5-/- mice developed LTi-like cell aggregates that were displaced from their typical niche at the intestinal crypt, and LTi-like cell hyperresponsiveness was associated with the local formation of this unconventional SILT. Thus, LTi-like cell positioning within mucosa controls their activity via niche-specific signals that temper cytokine production during homeostasis.

Keywords: CXCR5; innate lymphoid cells; intestine; lymphoid tissue; mucosal immunity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Gene Deletion
  • Immunity, Innate*
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukins / genetics
  • Interleukins / immunology*
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Lymphocytes / cytology
  • Lymphocytes / immunology*
  • Mice
  • Mice, Knockout
  • Receptors, CXCR5 / genetics
  • Receptors, CXCR5 / immunology*

Substances

  • CXCR5 protein, mouse
  • Il17a protein, mouse
  • Interleukin-17
  • Interleukins
  • Receptors, CXCR5
  • interleukin-22