Deletion of IRF4 in Dendritic Cells Leads to Delayed Onset of T Cell-Dependent Colitis
(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.
(Less)
- author
- Pool, Lieneke LU ; Rivollier, Aymeric LU and Agace, William W LU
- organization
- publishing date
- 2020-02-15
- type
- Contribution to journal
- publication status
- published
- subject
- 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}}, }