Year: 2025
Type: article
Abstract: Description The etiology of Inflammatory Bowel Disease is a dysregulated immune response to the intestinal microbiota in genetically predisposed individuals. At homeostasis, there is balance of regulatory T (Treg) cells and CD4+ effector T (TE) cells. During inflammation, this balance is lost, allowing excessive TE proliferation and inflammatory cytokine production. Therefore, we hypothesized that by increasing the ratio of Treg cells relative to TE cells, development of colitis could be prevented. So, we utilized a mutant IL-2 protein (IL-2M) that preferentially induces Tregs over effector cells, including CD4+ TE, CD8+ and NK cells. We found that IL-2M was superior at inducing Tregs in vivo compared to wild-type IL-2 (WTIL-2), in both C57BL/6 and CBir1Tg mice. Additionally, at the same molarity, IL-2M induced more Foxp3- IL-10+ cells. Using an adoptive CD4+ T cell transfer model of murine colitis, we tested the ability of Treg cells induced by IL-2M versus WTIL-2 to prevent colitis development. The co-transfer of naïve CBir1Tg CD4+ T cells and Treg cells induced in CBir1Tg mice by IL-2M at 1:1 ratio caused less severe colitis, when compared to co-transfer with Treg cells induced with WTIL-2. We observed less weight loss, splenomegaly, and intestinal inflammation in recipient mice treated with IL-2M induced Treg cells. In summary, our results show IL-2M can induce more Treg and Tr1 cells with greater stability, suggesting potential clinical therapeutics for IBD. Funding Sources This research was funded by a research grant from Merck & Co., Inc., Rahway, NJ, USA. Topic Categories Mucosal and Regional Immunology (MUC)
Source: The Journal of Immunology
Authors: Leighann Morgan, Shiuli Agarwal, Gretchen Baltus, Qing Zhao, Charles O. Elson
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416446807
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