Diverse developmental pathways of intestinal intraepithelial lymphocytes

Nat Rev Immunol. 2018 Aug;18(8):514-525. doi: 10.1038/s41577-018-0013-7.

Abstract

The intestinal epithelial barrier is patrolled by resident intraepithelial lymphocytes (IELs) that are involved in host defence against pathogens, wound repair and homeostatic interactions with the epithelium, microbiota and nutrients. Intestinal IELs are one of the largest populations of lymphocytes in the body and comprise several distinct subsets, the identity and lineage relationships of which have long remained elusive. Here, we review advances in unravelling the complexity of intestinal IEL populations, which comprise conventional αβ T cell receptor (TCRαβ)+ subsets, unconventional TCRαβ+ and TCRγδ+ subsets, group 1 innate lymphoid cells (ILC1s) and ILC1-like cells. Although these intestinal IEL lineages have partially overlapping effector programmes and recognition properties, they have strikingly different developmental pathways. We suggest that evolutionary pressure has driven the recurrent generation of cytolytic effector lymphocytes to protect the intestinal epithelial layer, but they may also precipitate intestinal inflammatory disorders, such as coeliac disease.

Publication types

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

MeSH terms

  • Animals
  • Celiac Disease / immunology
  • Cell Differentiation / immunology
  • Cell Lineage / immunology
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Immunity, Innate
  • Inflammatory Bowel Diseases / immunology
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / immunology*
  • Intraepithelial Lymphocytes / cytology*
  • Intraepithelial Lymphocytes / immunology*
  • Ligands
  • Mice
  • Models, Immunological
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology

Substances

  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Ligands
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta