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Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice
Published on: December 16, 2021
Transcriptional modulation of pattern recognition receptors in chronic colitis in mice is accompanied with Th1 and
Bin Zheng1, Mary E Morgan1, Hendrik J G van de Kant1
1Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht 3586 CG, The Netherlands.
Abstract:
Pattern recognition receptors (PRRs) may contribute to inflammatory bowel diseases (IBD) development due to their microbial-sensing ability and the unique microenvironment in the inflamed gut. In this study, the PRR mRNA expression profile together with T cell-associated factors in the colon was examined using a chronic colitis mice model. 8-12 week old C57BL/6 mice were exposed to multiple dextran sodium sulfate (DSS) treatments interspersed with a rest period to mimic the course of chronic colitis. The clinical features and histological data were collected. The mRNA expressions of colonic PRRs, T cell-associated components were measured. Finally, the colons were scored for Foxp3+ cells. During chronic colitis, the histological data, but not the clinical manifestations demonstrated characteristic inflammatory symptoms in the distal colon. In contrast to acute colitis, the expression of all Toll-like receptors (Tlrs), except Tlr5 and Tlr9, was unaffected after repeated DSS treatments. The expression of Nod1 was decreased, while Nod2 increased. After third DSS treatment, only the expressions of Tlr3 and Tlr4 were significantly enhanced. Unlike other PRRs, decreased Tlr5 and increased Tlr9 mRNA expression persisted during the chronic colitis period. As the colitis progress, only the mRNA expression of Ifnγ and Il17 staid increased during chronic colitis, while the acute colitis-associated increase of Il23, and Il10 and Il12 was abolished. Finally, increased histological score of Foxp3+ cell in colon was found during the chronic colitis period. This study provides an expression pattern of PRRs during chronic colitis that is accompanied by a Th1- and Th17 cell-mediated immune response.
Insights
Pattern recognition receptors (PRRs) expression changes in chronic colitis models reveal a persistent Th1 and Th17 immune response. This study highlights specific PRR alterations during chronic inflammation in the gut.
Area of Science:
- Immunology
- Gastroenterology
Background:
- Pattern recognition receptors (PRRs) sense microbes and may influence inflammatory bowel diseases (IBD).
- The gut microenvironment in IBD is unique and can impact PRR function.
Purpose of the Study:
- To investigate the mRNA expression profile of PRRs in the colon during chronic colitis.
- To examine T cell-associated factors and Foxp3+ cell infiltration in a chronic colitis mouse model.
Main Methods:
- A chronic colitis mouse model was established using repeated dextran sodium sulfate (DSS) treatments.
- Colonic mRNA expression of PRRs and T cell factors was measured.
- Histological analysis and Foxp3+ cell scoring were performed.
Main Results:
- Chronic colitis showed histological inflammation, but not clinical symptoms.
- Nod1 decreased while Nod2 increased; Tlr3 and Tlr4 were enhanced after the third DSS treatment.
- Tlr5 mRNA decreased and Tlr9 increased persistently during chronic colitis.
- Ifnγ and Il17 mRNA remained elevated, while Il23, Il10, and Il12 increases were abolished.
- Foxp3+ cell infiltration in the colon was increased.
Conclusions:
- Chronic colitis is characterized by specific PRR expression patterns, including persistent decreases in Tlr5 and increases in Tlr9.
- The immune response in chronic colitis involves elevated Ifnγ and Il17, indicating a Th1 and Th17 cell-mediated response.
- Increased Foxp3+ cells suggest a role for regulatory T cells in chronic gut inflammation.
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