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An IL-27/Lag3 axis enhances Foxp3+ regulatory T cell-suppressive function and therapeutic efficacy.
| Content Provider | Europe PMC |
|---|---|
| Author | Do, Jeong-su Visperas, Anabelle Sanogo, Yibayiri Osee Bechtel, Jennifer J. Dvorina, Nina Kim, Sohee Jang, Eunjung Stohlman, Stephen A. Shen, Bo Fairchild, Robert L. Baldwin, William M. Vignali, Dario A. A. Min, Booki |
| Abstract | Foxp3-expressing regulatory T cells (Tregs) are central regulators of immune homeostasis and tolerance. As it has been suggested that proper Treg function is compromised under inflammatory conditions, seeking for a pathway that enhances or stabilizes Treg function is a subject of considerable interest. We report that IL-27, an IL-12 family cytokine known to have both pro- and anti inflammatory roles in T cells, plays a pivotal role in enhancing Treg function to control T cell-induced colitis, a model for inflammatory bowel disease (IBD) in humans. Unlike wild type (WT) Tregs capable of inhibiting colitogenic T cell expansion and inflammatory cytokine expression, IL-27R-deficient Tregs were unable to downregulate inflammatory T cell responses. Tregs stimulated with IL-27 expressed substantially improved suppressive function in vitro and in vivo. IL-27 stimulation of Tregs induced expression of Lag3, a surface molecule implicated in negatively regulating immune responses. Lag3 expression in Tregs was critical to mediate Treg function in suppressing colitogenic responses. Human Tregs also displayed enhanced suppressive function and Lag3 expression following IL-27 stimulation. Collectively, these results highlight a novel function for the IL-27/Lag3 axis in modulating Treg regulation of inflammatory responses in the intestine. |
| Related Links | https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC4662649&blobtype=pdf |
| ISSN | 19330219 |
| Journal | Mucosal immunology [Mucosal Immunol] |
| Volume Number | 9 |
| DOI | 10.1038/mi.2015.45 |
| PubMed Central reference number | PMC4662649 |
| Issue Number | 1 |
| PubMed reference number | 26013006 |
| e-ISSN | 19353456 |
| Language | English |
| Publisher Date | 2015-05-27 |
| Access Restriction | Open |
| Rights License | Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| Subject Keyword | CD4 colitis IBD Interleukin-27 Lymphocyte activation gene 3 Treg |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
