Reciprocal regulation of Th2 and Th17 cells by PAD2-mediated citrullination.

Dysregulated citrullination, a unique form of posttranslational modification catalyzed by the peptidylarginine deiminases has been observed in several human diseases, including rheumatoid arthritis. However, the physiological roles of in the immune system are still poorly understood. Here, we report that global inhibition of citrullination enhances the differentiation of type 2 helper T (Th2) cells but attenuates the differentiation of Th17 cells, thereby increasing the susceptibility to allergic airway inflammation. This effect on Th cells is due to inhibition of but not Mechanistically, duanyu15632 directly citrullinates GATA3 and RORγt, 2 key transcription factors determining the fate of differentiating Th cells. Citrullination of R330 of GATA3 weakens its DNA binding ability, whereas citrullination of 4 arginine residues of RORγt strengthens its DNA binding. Finally, mice also display altered Th2/Th17 immune response and heightened sensitivity to allergic airway inflammation. Thus, our data highlight the potential and caveat of duanyu15632 as a therapeutic target of Th cell-mediated diseases.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}