Understanding the role of hnRNPA1 on T cell differentiation

Abstract

Abstract Regulatory T cells (Treg) play a critical role in preventing autoimmunity diseases and maintaining tolerance in various tissues, particularly the gut. Peripheral derived Tregs (pTregs) are especially crucial in gut homeostasis and tolerance to commensal and food antigens. We have previously shown that knockdown of the RNA-binding protein, heterogeneous nuclear ribonucleoprotein (hnRNP) A1, reduces in vitro pTreg induction upon low TCR stimulation. In addition, we have shown that, under conditions of low TCR stimulation, in which pTregs are induced, hnRNP A1 is phosphorylated by Akt. In order to explore the impact of hnRNP A1 phosphorylation by Akt on pTregs induction we have generated a mutant mouse model, hnRNPA1-S199 in which the known Akt phosphorylation site on hnRNP A1 is mutated to Alanine. We have examined the induction of pTregs in vivo using an adoptive transfer model of OT-II TCR transgenic mutant (hnRNPA1-S199A) and wild-type naïve CD4 T cells followed by oral OVA administration. In addition, we are examining the induction of pTregs in vitro using OVA peptide presented by wild-type and mutant (antigen presenting cells) APC from the spleen. Preliminary data showed a decrease in pTreg induction and proliferation when naïve mutant T cells are stimulated either in vitro or in vivo with OVA. Furthermore, we observe that mutant APC have a reduced ability to induce proliferation and pTreg induction in both mutant and WT T cells. These data suggest that hnRNP A1 has important functions in both T cells induction and antigen presentation.