T-bet-expressing Tr1 cells driven by dietary signals dominate the small intestinal immune landscape
Ansaldo, Eduard ; Yong, Daniel ; Carrillo, Nathan ; McFadden, Taryn ; Abid, Mahnoor ; Corral, Dan ; Rivera, Claudia ; Farley, Taylor ; Bouladoux, Nicolas and Gribonika, Inta LU
, et al.
(2026)
In Proceedings of the National Academy of Sciences of the United States of America
123(2).
- Abstract
Intestinal immunity defends against enteric pathogens, mediates symbiotic relationships with the resident microbiota, and provides tolerance to food antigens, safeguarding critical nutrient absorption and barrier functions of this mucosal tissue. Despite the abundance of tissue resident activated T cells, their contributions to these various roles remain poorly understood. Here, we identify a dominant population of IL-10 producing, T-bet-expressing Tr1 T cells, residing in the small intestinal lamina propria at homeostasis. Remarkably, these intestinal Tr1 cells emerge at the time of weaning and accumulate independently of the microbiota displaying similar abundance, function, and TCR repertoire under germ-free conditions. Instead, the... (More)
Intestinal immunity defends against enteric pathogens, mediates symbiotic relationships with the resident microbiota, and provides tolerance to food antigens, safeguarding critical nutrient absorption and barrier functions of this mucosal tissue. Despite the abundance of tissue resident activated T cells, their contributions to these various roles remain poorly understood. Here, we identify a dominant population of IL-10 producing, T-bet-expressing Tr1 T cells, residing in the small intestinal lamina propria at homeostasis. Remarkably, these intestinal Tr1 cells emerge at the time of weaning and accumulate independently of the microbiota displaying similar abundance, function, and TCR repertoire under germ-free conditions. Instead, the small intestinal T-bet+ Tr1 program is driven and shaped by dietary antigens, and accumulates in a cDC1-IL-27-dependent manner. Upon activation, these cells robustly express IL-10 and multiple inhibitory receptors, establishing a distinct suppressive profile. Altogether, this work uncovers a previously unappreciated dominant player in homeostatic small intestinal immunity with the potential to play critical suppressive roles in this tissue, raising important implications for the understanding of immune regulation in the intestine.
(Less)
- author
- Ansaldo, Eduard
; Yong, Daniel
; Carrillo, Nathan
; McFadden, Taryn
; Abid, Mahnoor
; Corral, Dan
; Rivera, Claudia
; Farley, Taylor
; Bouladoux, Nicolas
and Gribonika, Inta
LU
, et al. (More)
- Ansaldo, Eduard
; Yong, Daniel
; Carrillo, Nathan
; McFadden, Taryn
; Abid, Mahnoor
; Corral, Dan
; Rivera, Claudia
; Farley, Taylor
; Bouladoux, Nicolas
; Gribonika, Inta
LU
and Belkaid, Yasmine
(Less)
- publishing date
- 2026-01-13
- type
- Contribution to journal
- publication status
- published
- keywords
- Animals, Mice, Intestine, Small/immunology, Interleukin-10/metabolism, T-Box Domain Proteins/metabolism, T-bet Transcription Factor, Intestinal Mucosa/immunology, T-Lymphocytes, Regulatory/immunology, Homeostasis, Mice, Inbred C57BL, Diet, Immunity, Mucosal
- in
- Proceedings of the National Academy of Sciences of the United States of America
- volume
- 123
- issue
- 2
- article number
- e2520747122
- publisher
- National Academy of Sciences
- external identifiers
-
- scopus:105026951662
- pmid:41499395
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.2520747122
- language
- English
- LU publication?
- no
- id
- 5dd85bc0-f4f5-4e1f-8741-bfdfe16bc143
- date added to LUP
- 2026-01-12 11:37:04
- date last changed
- 2026-02-04 04:01:18
@article{5dd85bc0-f4f5-4e1f-8741-bfdfe16bc143,
abstract = {{<p>Intestinal immunity defends against enteric pathogens, mediates symbiotic relationships with the resident microbiota, and provides tolerance to food antigens, safeguarding critical nutrient absorption and barrier functions of this mucosal tissue. Despite the abundance of tissue resident activated T cells, their contributions to these various roles remain poorly understood. Here, we identify a dominant population of IL-10 producing, T-bet-expressing Tr1 T cells, residing in the small intestinal lamina propria at homeostasis. Remarkably, these intestinal Tr1 cells emerge at the time of weaning and accumulate independently of the microbiota displaying similar abundance, function, and TCR repertoire under germ-free conditions. Instead, the small intestinal T-bet+ Tr1 program is driven and shaped by dietary antigens, and accumulates in a cDC1-IL-27-dependent manner. Upon activation, these cells robustly express IL-10 and multiple inhibitory receptors, establishing a distinct suppressive profile. Altogether, this work uncovers a previously unappreciated dominant player in homeostatic small intestinal immunity with the potential to play critical suppressive roles in this tissue, raising important implications for the understanding of immune regulation in the intestine.</p>}},
author = {{Ansaldo, Eduard and Yong, Daniel and Carrillo, Nathan and McFadden, Taryn and Abid, Mahnoor and Corral, Dan and Rivera, Claudia and Farley, Taylor and Bouladoux, Nicolas and Gribonika, Inta and Belkaid, Yasmine}},
issn = {{1091-6490}},
keywords = {{Animals; Mice; Intestine, Small/immunology; Interleukin-10/metabolism; T-Box Domain Proteins/metabolism; T-bet Transcription Factor; Intestinal Mucosa/immunology; T-Lymphocytes, Regulatory/immunology; Homeostasis; Mice, Inbred C57BL; Diet; Immunity, Mucosal}},
language = {{eng}},
month = {{01}},
number = {{2}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences of the United States of America}},
title = {{T-bet-expressing Tr1 cells driven by dietary signals dominate the small intestinal immune landscape}},
url = {{http://dx.doi.org/10.1073/pnas.2520747122}},
doi = {{10.1073/pnas.2520747122}},
volume = {{123}},
year = {{2026}},
}