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IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis

Luda, Katarzyna M. LU ; Joeris, Thorsten LU ; Persson, Emma K. LU ; Rivollier, Aymeric LU ; Demiri, Mimoza LU ; Sitnik, Katarzyna M. LU ; Pool, Lieneke LU ; Holm, Jacob B.; Melo-Gonzalez, Felipe and Richter, Lisa, et al. (2016) In Immunity 44(4). p.860-874
Abstract

The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence of SI CD8αβ+ and CD4+CD8αα+ T cells; the latter requiring β8 integrin expression by migratory IRF8 dependent CD103+CD11b- DCs. SI homing receptor induction was impaired during T cell priming in mesenteric lymph nodes (MLN), which correlated with a reduction in aldehyde dehydrogenase activity by SI-derived MLN DCs, and inefficient T cell localization to the SI. These mice also lacked intestinal... (More)

The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence of SI CD8αβ+ and CD4+CD8αα+ T cells; the latter requiring β8 integrin expression by migratory IRF8 dependent CD103+CD11b- DCs. SI homing receptor induction was impaired during T cell priming in mesenteric lymph nodes (MLN), which correlated with a reduction in aldehyde dehydrogenase activity by SI-derived MLN DCs, and inefficient T cell localization to the SI. These mice also lacked intestinal T helper 1 (Th1) cells, and failed to support Th1 cell differentiation in MLN and mount Th1 cell responses to Trichuris muris infection. Collectively these results highlight multiple non-redundant roles for IRF8 dependent DCs in the maintenance of intestinal T cell homeostasis.

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type
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publication status
published
subject
in
Immunity
volume
44
issue
4
pages
15 pages
publisher
Cell Press
external identifiers
  • Scopus:84962173629
ISSN
1074-7613
DOI
10.1016/j.immuni.2016.02.008
language
English
LU publication?
no
id
db00b0a5-ed63-4618-a677-6eba162bd14e
date added to LUP
2016-05-31 12:43:19
date last changed
2016-11-27 04:40:44
@misc{db00b0a5-ed63-4618-a677-6eba162bd14e,
  abstract     = {<p>The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence of SI CD8αβ<sup>+</sup> and CD4<sup>+</sup>CD8αα<sup>+</sup> T cells; the latter requiring β8 integrin expression by migratory IRF8 dependent CD103<sup>+</sup>CD11b<sup>-</sup> DCs. SI homing receptor induction was impaired during T cell priming in mesenteric lymph nodes (MLN), which correlated with a reduction in aldehyde dehydrogenase activity by SI-derived MLN DCs, and inefficient T cell localization to the SI. These mice also lacked intestinal T helper 1 (Th1) cells, and failed to support Th1 cell differentiation in MLN and mount Th1 cell responses to Trichuris muris infection. Collectively these results highlight multiple non-redundant roles for IRF8 dependent DCs in the maintenance of intestinal T cell homeostasis.</p>},
  author       = {Luda, Katarzyna M. and Joeris, Thorsten and Persson, Emma K. and Rivollier, Aymeric and Demiri, Mimoza and Sitnik, Katarzyna M. and Pool, Lieneke and Holm, Jacob B. and Melo-Gonzalez, Felipe and Richter, Lisa and Lambrecht, Bart N. and Kristiansen, Karsten and Travis, Mark A. and Svensson-Frej, Marcus and Kotarsky, Knut and Agace, William W.},
  issn         = {1074-7613},
  language     = {eng},
  month        = {04},
  number       = {4},
  pages        = {860--874},
  publisher    = {ARRAY(0x9bee098)},
  series       = {Immunity},
  title        = {IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis},
  url          = {http://dx.doi.org/10.1016/j.immuni.2016.02.008},
  volume       = {44},
  year         = {2016},
}