Tregs are dysfunctional in vivo in a spontaneous murine model of Crohn's disease
| Autor: | Daniele Corridoni, Wei Xin, Kristen O. Arseneau, Theresa T. Pizarro, Li-Guo Jia, Dai Ishikawa, Fabio Cominelli, Xiao-Ming Wang, A. Okazawa, Mitchell Guanzon |
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| Rok vydání: | 2013 |
| Předmět: |
Crohn’s disease
CD4-Positive T-Lymphocytes Adoptive cell transfer Time Factors Immunology chemical and pharmacologic phenomena Biology T-Lymphocytes Regulatory Inflammatory bowel disease Article regulatory T cells Lymphocyte Depletion Proinflammatory cytokine Mice 03 medical and health sciences Th2 Cells 0302 clinical medicine Crohn Disease CD25+Foxp3+ medicine Animals Immunology and Allergy Ileitis IL-2 receptor SAMP1/YitFc Colitis 030304 developmental biology 0303 health sciences Interleukin-17 Interleukin-2 Receptor alpha Subunit Antibodies Monoclonal FOXP3 Forkhead Transcription Factors hemic and immune systems Th1 Cells medicine.disease Adoptive Transfer 3. Good health Disease Models Animal Cytokines Female Interleukin 17 030215 immunology |
| Zdroj: | Mucosal immunology |
| ISSN: | 1933-0219 |
| DOI: | 10.1038/mi.2012.67 |
| Popis: | Although regulatory T cells (Tregs) have been implicated in inflammatory bowel disease, Tregs from Crohn's disease (CD) patients are increased in number and function normally in vitro. To clarify this disparity, we studied Treg function in vivo using a spontaneous model of CD-like ileitis. We first administered anti-CD25-depleting antibodies to SAMP1/YitFc (SAMP) mice to assess ileitis; mesenteric lymph node cells were then transferred into SCID (severe combined immunodeficient) recipients to induce colitis. CD25 depletion increased the severity of both spontaneous ileitis and adoptively transferred colitis. Interestingly, a second transfer of CD4(+)CD25(+) cells from untreated AKR control mice was able to ameliorate the induced colitis, whereas CD4(+)CD25(+) cells from untreated SAMP mice were not, suggesting a functional abnormality in SAMP Tregs. Anti-CD25 treatment in SAMP mice also induced proliferation of CD25(-)Foxp3(+) Tregs, which had a proinflammatory intestinal T helper type 1/ T helper type 2 (Th1/Th2) effector phenotype. These studies demonstrate Treg dysfunction in a spontaneous model of CD-like ileitis. |
| Databáze: | OpenAIRE |
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