Stacey Harbour, Ph.D., Scientist I, Anatomic Pathology, in the lab of Casey Weaver, M.D., Professor, Anatomic Pathology, published an article on T cell differentiation in the July issue of Science Immunology, titled, "T_H17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity."

Research conducted by the group showed that the molecule IL-6, a common target of various disease therapies, was indispensable for maintaining the inflammatory effects of T helper 17 cells that are implicated in diseases like IBD and psoriasis.

The article is published with co-authors Robin Hatton, Ph.D., Associate Professor, Anatomic Pathology; Daniel DiToro, Ph.D., Graduate Student, Anatomic Pathology; Steven Witte, Ph.D., Consultant, Anatomic Pathology; Carlene Zindl, Scientist I, Anatomic Pathology; Min Gao, Ph.D., Assistant Professor, Medicine; Trenton Schoeb, Ph.D., Professor, Genetics.

From the article:

"The pathogenic role of the T_H17 subset of CD4⁺ T cells in multiple immune-mediated diseases has prompted close scrutiny of the cytokine signals that promote differentiation and maintenance of T_H17 cells. IL-6 and TGF-β are key cytokines for T_H17 commitment by naïve T cells whereas IL-23 supports maintenance of a T_H17 identity. Harbour et al. investigated whether persistent IL-6 signaling is also needed to sustain T_H17 cell functions. IL-6Rα–deficient mouse T cells could not maintain a T_H17 phenotype and were attenuated in their ability to elicit colitis in an in vivo cell transfer model. These studies provide deeper insights into the set of signals required for T_H17 cell maintenance and suggest additional molecular targets for pharmacological interventions aimed at antagonizing pathogenic T_H17 immunity.

Acting in concert with TGF-β, interleukin-6 (IL-6) signaling induces T helper 17 (TH17) cell development by programming TH17-related genes via signal transducers and activators of transcription 3 (STAT3). A role for IL-6 signaling beyond the inductive phase of TH17 cell development has not been defined because IL-23 signaling downstream of TH17 cell induction also activates STAT3 and is thought responsible for TH17 cell maintenance. Here, we find that IL-6 signaling is required for both induction and maintenance of mouse TH17 cells; IL-6Rα–deficient TH17 cells rapidly lost their TH17 phenotype and did not cause disease in two models of colitis. Cotransfer of wild-type TH17 cells with IL-6Rα–deficient TH17 cells induced colitis but was unable to rescue phenotype loss of the latter. High IL-6 expression in the colon promoted classic, or cis, rather than transreceptor signaling that was required for maintenance of TH17 cells. Thus, ongoing classic IL-6 signaling underpins the TH17 program and is required for TH17 cell maintenance and function."

Look for a full news release to come.