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Deletion of IRF4 in Dendritic Cells Leads to Delayed Onset of T Cell-Dependent Colitis

Pool, Lieneke LU ; Rivollier, Aymeric LU and Agace, William W LU (2020) In Journal of immunology 204(4). p.1047-1055
Abstract

Classical dendritic cells (cDC) can be classified into two major subsets: Irf8-dependent cDC1 and Irf4-expressing cDC2. Although these subsets play distinct roles in intestinal immune homeostasis, their functions in T cell-driven colitis remain unknown. To assess the role of IRF4 expression in cDC2 in T cell-driven colitis, CD11c-Cre.Irf4fl/fl and Irf4fl/fl mice were backcrossed onto a Rag-1-/- background and used as recipients of CD45RBhiCD4+ T cells. Colitis score and innate immune cell influx were reduced in Cre+ mice 4 wk posttransfer, and these changes were associated with reduced CD4+ T cell counts in both the mesenteric lymph nodes and colon. By 7 wk, colitis score and colon CD4+ T cell numbers were similar in Cre+ and Cre- mice... (More)

Classical dendritic cells (cDC) can be classified into two major subsets: Irf8-dependent cDC1 and Irf4-expressing cDC2. Although these subsets play distinct roles in intestinal immune homeostasis, their functions in T cell-driven colitis remain unknown. To assess the role of IRF4 expression in cDC2 in T cell-driven colitis, CD11c-Cre.Irf4fl/fl and Irf4fl/fl mice were backcrossed onto a Rag-1-/- background and used as recipients of CD45RBhiCD4+ T cells. Colitis score and innate immune cell influx were reduced in Cre+ mice 4 wk posttransfer, and these changes were associated with reduced CD4+ T cell counts in both the mesenteric lymph nodes and colon. By 7 wk, colitis score and colon CD4+ T cell numbers were similar in Cre+ and Cre- mice despite a selective reduction in Th17 cells in the colon of Cre+ mice and a continued reduction in CD4+ T cell numbers in mesenteric lymph nodes. Cotransfer of CD25+CD45RBlo CD4+ T cells prevented CD45RBhiCD4+ T cell-driven colitis in both Cre+ and Cre- recipients, demonstrating that IRF4 expression by cDC is not required for CD4+ regulatory T cell-mediated control of colitis. Collectively these results suggest a role for IRF4 expression in cDC2 in the generation of colitogenic CD4+ T cells, which becomes redundant as colitis progresses.

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publication status
published
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in
Journal of immunology
volume
204
issue
4
pages
9 pages
publisher
American Association of Immunologists
external identifiers
  • scopus:85079019866
  • pmid:31900340
ISSN
1550-6606
DOI
10.4049/jimmunol.1900775
language
English
LU publication?
yes
additional info
Copyright © 2020 by The American Association of Immunologists, Inc.
id
5026349a-9a84-4cb8-a056-d93df56efe2f
date added to LUP
2020-01-27 17:08:28
date last changed
2024-06-27 12:14:28
@article{5026349a-9a84-4cb8-a056-d93df56efe2f,
  abstract     = {{<p>Classical dendritic cells (cDC) can be classified into two major subsets: Irf8-dependent cDC1 and Irf4-expressing cDC2. Although these subsets play distinct roles in intestinal immune homeostasis, their functions in T cell-driven colitis remain unknown. To assess the role of IRF4 expression in cDC2 in T cell-driven colitis, CD11c-Cre.Irf4fl/fl and Irf4fl/fl mice were backcrossed onto a Rag-1-/- background and used as recipients of CD45RBhiCD4+ T cells. Colitis score and innate immune cell influx were reduced in Cre+ mice 4 wk posttransfer, and these changes were associated with reduced CD4+ T cell counts in both the mesenteric lymph nodes and colon. By 7 wk, colitis score and colon CD4+ T cell numbers were similar in Cre+ and Cre- mice despite a selective reduction in Th17 cells in the colon of Cre+ mice and a continued reduction in CD4+ T cell numbers in mesenteric lymph nodes. Cotransfer of CD25+CD45RBlo CD4+ T cells prevented CD45RBhiCD4+ T cell-driven colitis in both Cre+ and Cre- recipients, demonstrating that IRF4 expression by cDC is not required for CD4+ regulatory T cell-mediated control of colitis. Collectively these results suggest a role for IRF4 expression in cDC2 in the generation of colitogenic CD4+ T cells, which becomes redundant as colitis progresses.</p>}},
  author       = {{Pool, Lieneke and Rivollier, Aymeric and Agace, William W}},
  issn         = {{1550-6606}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{4}},
  pages        = {{1047--1055}},
  publisher    = {{American Association of Immunologists}},
  series       = {{Journal of immunology}},
  title        = {{Deletion of IRF4 in Dendritic Cells Leads to Delayed Onset of T Cell-Dependent Colitis}},
  url          = {{http://dx.doi.org/10.4049/jimmunol.1900775}},
  doi          = {{10.4049/jimmunol.1900775}},
  volume       = {{204}},
  year         = {{2020}},
}