Calcineurin-mediated IL-2 production by CD11c(high)MHCII(+) myeloid cells is crucial for intestinal immune homeostasis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F18%3A00068615" target="_blank" >RIV/00159816:_____/18:00068615 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41467-018-03495-3" target="_blank" >https://www.nature.com/articles/s41467-018-03495-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-018-03495-3" target="_blank" >10.1038/s41467-018-03495-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Calcineurin-mediated IL-2 production by CD11c(high)MHCII(+) myeloid cells is crucial for intestinal immune homeostasis

Popis výsledku v původním jazyce

The intestinal immune system can respond to invading pathogens yet maintain immune tolerance to self-antigens and microbiota. Myeloid cells are central to these processes, but the signaling pathways that underlie tolerance versus inflammation are unclear. Here we show that mice lacking Calcineurin B in CD11c(high)MHCII(+) cells (Cnb1(CD11c) mice) spontaneously develop intestinal inflammation and are susceptible to induced colitis. In these mice, colitis is associated with expansion of T helper type 1 (Th1) and Th17 cell populations and a decrease in the number of FoxP3(+) regulatory T (Treg) cells, and the pathology is linked to the inability of intestinal Cnb1-deficient CD11c(high)MHCII(+) cells to express IL-2. Deleting IL-2 in CD11c(high)MHCII(+) cells induces spontaneous colitis resembling human inflammatory bowel disease. Our findings identify that the calcineurin-NFAT-IL-2 pathway in myeloid cells is a critical regulator of intestinal homeostasis by influencing the balance of inflammatory and regulatory responses in the mouse intestine.

Název v anglickém jazyce

Calcineurin-mediated IL-2 production by CD11c(high)MHCII(+) myeloid cells is crucial for intestinal immune homeostasis

Popis výsledku anglicky

The intestinal immune system can respond to invading pathogens yet maintain immune tolerance to self-antigens and microbiota. Myeloid cells are central to these processes, but the signaling pathways that underlie tolerance versus inflammation are unclear. Here we show that mice lacking Calcineurin B in CD11c(high)MHCII(+) cells (Cnb1(CD11c) mice) spontaneously develop intestinal inflammation and are susceptible to induced colitis. In these mice, colitis is associated with expansion of T helper type 1 (Th1) and Th17 cell populations and a decrease in the number of FoxP3(+) regulatory T (Treg) cells, and the pathology is linked to the inability of intestinal Cnb1-deficient CD11c(high)MHCII(+) cells to express IL-2. Deleting IL-2 in CD11c(high)MHCII(+) cells induces spontaneous colitis resembling human inflammatory bowel disease. Our findings identify that the calcineurin-NFAT-IL-2 pathway in myeloid cells is a critical regulator of intestinal homeostasis by influencing the balance of inflammatory and regulatory responses in the mouse intestine.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

<a href="/cs/project/EF15_003%2F0000492" target="_blank" >EF15_003/0000492: Mapování molekulární podstaty procesů stárnutí pro vývoj nových léčebných metod</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature Communications

ISSN

2041-1723

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

March

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

—

Kód UT WoS článku

000427591600002

EID výsledku v databázi Scopus

—