Hnrnp regulates the Treg cell population by maintaining Foxp3 expression 4684

Abstract Description Heterogeneous nuclear ribonucleoproteins (HNRNPs) are widely expressed RNA-binding proteins with essential roles in maintaining cellular homeostasis. To investigate their immunological functions, we focused on regulatory T cells (Tregs) which are critical for maintaining immune balance and preventing excessive T cell activation. Tregs are characterized by the continuous expression of the transcription factor Foxp3 which is necessary for its identity and homeostasis. Using a Foxp3-CRE/YFP mouse model, we knocked out specific Hnrnp genes in Tregs (Hnrnpfl/fl-Foxp3 Cre+/YFP, KO) and compared the results with controls (Hnrnpwt/fl-Foxp3 Cre+/YFP). The knockout led to an autoimmune-like disorder resembling the ‘Scurfy mice’ phenotype, which is characterized by lymphocytic infiltration, dermatitis, splenomegaly, enlarged lymph nodes, and thymic atrophy. Flow cytometry and RNA sequencing revealed that Hnrnp loss triggered a strong inflammatory response, marked by increased T helper cells and macrophages and a diminished Treg population. The absence of Hnrnp reduced Foxp3 RNA and protein levels, indicating its essential role in maintaining Foxp3 expression. In summary, our results highlight the crucial role of the Hnrnp family in preserving the identity of Tregs by influencing Foxp3 transcription. This insight could be vital for developing therapies targeting autoimmune diseases that rely on maintaining Foxp3 levels and mitigating inflammatory responses. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)