KLRG1 impairs regulatory T‐cell competitive fitness in the gut. Issue 1 (20th June 2017)

• Record Type: Journal Article
• Authors: Meinicke, Holger; Bremser, Anna; Brack, Maria; Schrenk, Klaudia; Pircher, Hanspeter; Izcue, Ana
• Is Part Of: Immunology. Volume 152:Issue 1(2017)
• Page Start: 65
• Page End: 73
• Publication Date: 2017-06-20
• Subjects: Foxp3 -- intestine -- KLRG1 -- T‐cell receptor; Immunology -- Periodicals
• DOI: 10.1111/imm.12749
• Languages: English
• ISSNs: 0019-2805

Abstract

Summary: 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. Abstract : The cadherin receptor KLRG1 is expressed by a subpopulation of effector Foxp3 + regulatory T (Treg) cells that is especially abundant in the gut. In this manuscript we use knockout mice to analyse the role of KLRG1 on Treg cells. Although KLRG1 is not required for Treg cell generation or function, KLRG1 cross‐linking dampens T‐cell receptor signals in vitro, and KLRG1 expression confers on Treg cells a competitive disadvantage in the gut but not in lymphoid organs.