Themis differentially regulates T follicular helper cell differentiation during early and late stages of chronic viral Infection

Yuzhen Zhu¹Yuzhou Bao¹Ning Wang¹Qifeng Gan¹Jian Tang¹Yu Cong¹Bowen Hou¹Quan Minxue¹Chaonan Yan¹Siyi Liu¹Shuo Lin¹Xiao-bin Zhang¹Yanping Du¹Lichao Hou¹Nicholas R J Gascoigne²BING XU¹GUO FU¹Qi-Fan Zheng^1*

• ¹Xiamen University, Xiamen, China
• ²Augusta University, Augusta, United States

TFH cells play an important role in chronic viral infection by helping B cells produce antibodies. Recent studies have identified a novel CD4 + T cell progenitor population in chronic LCMV infection that sustains the differentiation of TFH and other effector CD4 + T cells. However, the details of this differentiation process remain unclear. Here, we report an unprecedented dual role for Themis in regulating the differentiation of CD4 + T cell progenitors into TFH cells during chronic LCMV infection.Themis expression is strongly upregulated in TFH cells at early stages of infection, and as expected, Themis promotes TFH cell differentiation at this stage. However, unexpectedly, at the late stages of chronic LCMV infection, Themis-deficient CD4 + T cells favored TFH cell differentiation and helped 2 control the virus by enhancing GC responses and antibody production, suggesting that Themis inhibits TFH cell differentiation at this stage. In the late stage we found that Themis inhibits the differentiation of CD4 + T cell progenitors into TFH cells through transcriptional regulation.