CD4 T cells are required for both development and maintenance of disease in a new mouse model of reversible colitis

Brasseit, J.; Althaus-Steiner, E.; Faderl, M.; Dickgreber, N.; Saurer, L.; Genitsch, V.; Dolowschiak, T.; Li, Hai; Finke, D.; Hardt, W.-D.; McCoy, Kathleen; Macpherson, Andrew; Corazza, N.; Noti, M.; Mueller, C. (2016). CD4 T cells are required for both development and maintenance of disease in a new mouse model of reversible colitis. Mucosal immunology, 9(3), pp. 689-701. Nature Publishing Group 10.1038/mi.2015.93

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Current therapies to treat inflammatory bowel diseases have limited efficacy, significant side effects, and often wane over time. Little is known about the cellular and molecular mechanisms operative in the process of mucosal healing from colitis. To study such events, we developed a new model of reversible colitis in which adoptive transfer of CD4(+)CD45RB(hi) T cells into Helicobacter typhlonius-colonized lymphopenic mice resulted in a rapid onset of colonic inflammation that was reversible through depletion of colitogenic T cells. Remission was associated with an improved clinical and histopathological score, reduced immune cell infiltration to the intestinal mucosa, altered intestinal gene expression profiles, regeneration of the colonic mucus layer, and the restoration of epithelial barrier integrity. Notably, colitogenic T cells were not only critical for induction of colitis but also for maintenance of disease. Depletion of colitogenic T cells resulted in a rapid drop in tumor necrosis factor α (TNFα) levels associated with reduced infiltration of inflammatory immune cells to sites of inflammation. Although neutralization of TNFα prevented the onset of colitis, anti-TNFα treatment of mice with established disease failed to resolve colonic inflammation. Collectively, this new model of reversible colitis provides an important research tool to study the dynamics of mucosal healing in chronic intestinal remitting-relapsing disorders.Mucosal Immunology advance online publication 16 September 2015; doi:10.1038/mi.2015.93.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Brasseit, Jennifer; Faderl, Martin; Dickgreber, Nina; Saurer, Leslie; Genitsch Gratwohl, Vera; Li, Hai; McCoy, Kathleen; Macpherson, Andrew; Corazza, Nadia; Noti, Mario and Müller, Christoph

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1933-0219

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

07 Dec 2015 12:09

Last Modified:

15 Sep 2017 07:35

Publisher DOI:

10.1038/mi.2015.93

PubMed ID:

26376366

BORIS DOI:

10.7892/boris.73734

URI:

https://boris.unibe.ch/id/eprint/73734

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