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cDC1-derived IL-27 regulates small intestinal CD4+ T cell homeostasis in mice

Ahmadi, Fatemeh LU ; Junghus, Fredrik LU ; Ashworth, Christian LU ; Lappalainen, Amanda ; Mörbe, Urs LU ; Kotarsky, Knut LU and Agace, William W LU (2023) In The Journal of experimental medicine 220(3).
Abstract

The small intestinal lamina propria contains large numbers of IFNγ-producing T helper (Th1) cells that play important roles in intestinal homeostasis and host defense, but the mechanisms underlying their development remain poorly understood. Here, we demonstrate that Th1 cells accumulate in the SI-LP after weaning and are maintained there long term. While both Th17 and Th1 cell accumulation in the SI-LP was microbiota dependent, Th1 cell accumulation uniquely required IL-27 and MHCII expression by cDC1. This reflected a requirement for IL-27 signaling in the priming of Th1 cells rather than for their maintenance once in the mucosa. cDC1-derived IL-27 was essential for maintaining the Th1-Th17 balance within the SI-LP, and in its... (More)

The small intestinal lamina propria contains large numbers of IFNγ-producing T helper (Th1) cells that play important roles in intestinal homeostasis and host defense, but the mechanisms underlying their development remain poorly understood. Here, we demonstrate that Th1 cells accumulate in the SI-LP after weaning and are maintained there long term. While both Th17 and Th1 cell accumulation in the SI-LP was microbiota dependent, Th1 cell accumulation uniquely required IL-27 and MHCII expression by cDC1. This reflected a requirement for IL-27 signaling in the priming of Th1 cells rather than for their maintenance once in the mucosa. cDC1-derived IL-27 was essential for maintaining the Th1-Th17 balance within the SI-LP, and in its absence, remaining Th1 cells expressed enhanced levels of Th17 signature genes. In conclusion, we identify cDC1-derived IL-27 as a key regulator of SI-LP Th1-Th17 cell homeostasis.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Mice, Animals, CD4-Positive T-Lymphocytes/metabolism, Interleukin-27/metabolism, Interleukin-17/metabolism, Th17 Cells/metabolism, Th1 Cells/metabolism, Intestinal Mucosa/metabolism, Homeostasis
in
The Journal of experimental medicine
volume
220
issue
3
publisher
Rockefeller University Press
external identifiers
  • pmid:36515659
  • scopus:85150361135
ISSN
1540-9538
DOI
10.1084/jem.20221090
language
English
LU publication?
yes
additional info
© 2022 Ahmadi et al.
id
c6f12739-5d35-43c6-be54-9e9ec6aed8d5
date added to LUP
2023-01-27 21:20:23
date last changed
2024-05-17 23:43:34
@article{c6f12739-5d35-43c6-be54-9e9ec6aed8d5,
  abstract     = {{<p>The small intestinal lamina propria contains large numbers of IFNγ-producing T helper (Th1) cells that play important roles in intestinal homeostasis and host defense, but the mechanisms underlying their development remain poorly understood. Here, we demonstrate that Th1 cells accumulate in the SI-LP after weaning and are maintained there long term. While both Th17 and Th1 cell accumulation in the SI-LP was microbiota dependent, Th1 cell accumulation uniquely required IL-27 and MHCII expression by cDC1. This reflected a requirement for IL-27 signaling in the priming of Th1 cells rather than for their maintenance once in the mucosa. cDC1-derived IL-27 was essential for maintaining the Th1-Th17 balance within the SI-LP, and in its absence, remaining Th1 cells expressed enhanced levels of Th17 signature genes. In conclusion, we identify cDC1-derived IL-27 as a key regulator of SI-LP Th1-Th17 cell homeostasis.</p>}},
  author       = {{Ahmadi, Fatemeh and Junghus, Fredrik and Ashworth, Christian and Lappalainen, Amanda and Mörbe, Urs and Kotarsky, Knut and Agace, William W}},
  issn         = {{1540-9538}},
  keywords     = {{Mice; Animals; CD4-Positive T-Lymphocytes/metabolism; Interleukin-27/metabolism; Interleukin-17/metabolism; Th17 Cells/metabolism; Th1 Cells/metabolism; Intestinal Mucosa/metabolism; Homeostasis}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{3}},
  publisher    = {{Rockefeller University Press}},
  series       = {{The Journal of experimental medicine}},
  title        = {{cDC1-derived IL-27 regulates small intestinal CD4+ T cell homeostasis in mice}},
  url          = {{http://dx.doi.org/10.1084/jem.20221090}},
  doi          = {{10.1084/jem.20221090}},
  volume       = {{220}},
  year         = {{2023}},
}