A Murine Intestinal Intraepithelial NKp46-Negative Innate Lymphoid Cell Population Characterized by Group 1 Properties

Cell Rep. 2017 May 16;19(7):1431-1443. doi: 10.1016/j.celrep.2017.04.068.

Abstract

The Ly49E receptor is preferentially expressed on murine innate-like lymphocytes, such as epidermal Vγ3 T cells, intestinal intraepithelial CD8αα+ T lymphocytes, and CD49a+ liver natural killer (NK) cells. As the latter have recently been shown to be distinct from conventional NK cells and have innate lymphoid cell type 1 (ILC1) properties, we investigated Ly49E expression on intestinal ILC populations. Here, we show that Ly49E expression is very low on known ILC populations, but it can be used to define a previously unrecognized intraepithelial innate lymphoid population. This Ly49E-positive population is negative for NKp46 and CD8αα, expresses CD49a and CD103, and requires T-bet expression and IL-15 signaling for differentiation and/or survival. Transcriptome analysis reveals a group 1 ILC gene profile, different from NK cells, iCD8α cells, and intraepithelial ILC1. Importantly, NKp46-CD8αα-Ly49E+ cells produce interferon (IFN)-γ, suggesting that this previously unrecognized population may contribute to Th1-mediated immunity.

Keywords: IFN-γ; ILC1; Ly49E; NKp46-negative; intestinal; intraepithelial.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Ly / metabolism*
  • Cell Shape
  • Cytotoxicity, Immunologic
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Immunity, Innate*
  • Interferon-gamma / biosynthesis
  • Intestines / cytology*
  • Killer Cells, Natural / metabolism
  • Lymphocytes / cytology*
  • Lymphocytes / metabolism*
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily A / metabolism
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism*
  • Phenotype
  • Signal Transduction
  • Transcription Factors / metabolism
  • Transcriptome / genetics

Substances

  • Antigens, CD
  • Antigens, Ly
  • NK Cell Lectin-Like Receptor Subfamily A
  • Natural Cytotoxicity Triggering Receptor 1
  • Ncr1 protein, mouse
  • Transcription Factors
  • Interferon-gamma