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In PNAS Article, Karandikar Lab Demonstrates a Novel CD4 T-cell-intrinsic Function for Interleukin 17 Cytokines

July 31, 2020

Dr. Crawford Dr. Sinha Dr. Renavikar Dr. Borcherding Dr. Karandikar

Interleukin (IL)-17A is an important cytokine responsible for control of various microbial infections. IL-17A, IL-17F and the IL-17AF heterodimer are the signature cytokines produced by a particular type of CD4+ T-helper cell, designated as “Th17”. When dysregulated, Th17 cells and their cytokines contribute to the pathogenesis of autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease, among others. Thus far, research into the mechanisms of IL-17 action has focused on the effect of these cytokines on various cell types, including endothelial cells, epithelial cells, fibroblasts, neutrophils, monocytes/macrophages.

In a recent publication in the Proceedings of the National Academy of Sciences titled ‘CD4 T cell-intrinsic role for the T helper 17 signature cytokine IL-17: Effector resistance to immune suppression’, the Karandikar laboratory at the University of Iowa Department of Pathology demonstrated that these IL-17 cytokines are capable of acting directly on the CD4+ T-cells themselves, including not only Th17 cells, but also non-Th17 cells. Interestingly, the effect of this CD4-intrinsic action is to make the cells resistant to suppression by immune regulatory mechanisms, which may be beneficial in the case of infections, but severely detrimental in the context of autoimmune disease.

These studies also include mechanistic dissection of this effect through transcriptome analysis, revealing the interesting involvement of IL-1B and IL-6 pathways in this process, which would be an important focus of future research to uncover targetable pathways for treatment.

Michael Crawford, MD, is the lead author of the study. Co-authors include Drs. Sushmita Sinha, Pranav Renavikar, Nicholas Borcherding, and Nitin Karandikar.

View the online publication of this paper in the Proceedings of the National Academy of Sciences.