1. Academic Validation
  2. KLRG1 impairs regulatory T-cell competitive fitness in the gut

KLRG1 impairs regulatory T-cell competitive fitness in the gut

  • Immunology. 2017 Sep;152(1):65-73. doi: 10.1111/imm.12749.
Holger Meinicke 1 2 3 Anna Bremser 1 2 Maria Brack 1 2 Klaudia Schrenk 2 4 Hanspeter Pircher 5 Ana Izcue 1 2
Affiliations

Affiliations

  • 1 Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
  • 2 Centre for Chronic Immunodeficiency (CCI), University Medical Centre Freiburg and University of Freiburg, Freiburg, Germany.
  • 3 Department of Pediatrics and Adolescent Medicine, Division of General Pediatrics, University Medical Centre, Freiburg, Germany.
  • 4 Institute of Pathology, University of Freiburg, Freiburg, Germany.
  • 5 Institute of Immunology, University Medical Centre Freiburg, Freiburg, Germany.
Abstract

Immune homeostasis requires the tight, tissue-specific control of the different CD4+ Foxp3+ regulatory T (Treg) cell populations. The cadherin-binding inhibitory receptor killer cell lectin-like receptor G1 (KLRG1) is expressed by a subpopulation of Treg cells with GATA3+ effector phenotype. Although such Treg cells are important for the immune balance, especially in the gut, the role of KLRG1 in Treg cells has not been assessed. Using KLRG1 knockout mice, we found that KLRG1 deficiency does not affect Treg cell frequencies in spleen, mesenteric lymph nodes or intestine, or frequencies of GATA3+ Treg cells in the gut. KLRG1-deficient Treg cells were also protective in a T-cell transfer model of colitis. Hence, KLRG1 is not essential for the development or activity of the general Treg cell population. We then checked the effects of KLRG1 on Treg cell activation. In line with KLRG1's reported inhibitory activity, in vitro KLRG1 cross-linking dampened the Treg cell T-cell receptor response. Consistently, lack of KLRG1 on Treg cells conferred on them a competitive advantage in the gut, but not in lymphoid organs. Hence, although absence of KLRG1 is not enough to increase intestinal Treg cells in KLRG1 knockout mice, KLRG1 ligation reduces T-cell receptor signals and the competitive fitness of individual Treg cells in the intestine.

Keywords

Foxp3; KLRG1; T-cell receptor; intestine.

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