Transcription factor p73 regulates Th1 differentiation

Inter-individual differences in T helper (Th) cell responses affect susceptibility to infectious, allergic and autoimmune diseases. To identify factors contributing to these response differences, here we analyze in vitro differentiated Th1 cells from 16 inbred mouse strains. Haplotype-based computational genetic analysis indicates that the p53 family protein, p73, affects Th1 differentiation. In cells differentiated under Th1 conditions in vitro, p73 negatively regulates IFNγ production. p73 binds within, or upstream of, and modulates the expression of Th1 differentiation-related genes such as Ifng and Il12rb2. Furthermore, in mouse experimental autoimmune encephalitis, p73-deficient mice have increased IFNγ production and less disease severity, whereas in an adoptive transfer model of inflammatory bowel disease, transfer of p73-deficient naïve CD4+ T cells increases Th1 responses and augments disease severity. Our results thus identify p73 as a negative regulator of the Th1 immune response, suggesting that p73 dysregulation may contribute to susceptibility to autoimmune disease.


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Policy information about availability of data All manuscripts must include a data availability statement. This statement should provide the following information, where applicable: -Accession codes, unique identifiers, or web links for publicly available datasets -A list of figures that have associated raw data -A description of any restrictions on data availability No statistical method was used to predetermine sample size. For the EAE model, we included all available mice. For the IBD model, we followed standard protocols used by our collaborators, who are experts in this area. For all other experiments, we followed recommended sample size from well established protocols. All experiments were repeated, as indicated.
No data was excluded from this study. All fluorophore conjugated antibodies are against mouse protein and used for flow cytometry. Anti-FLAG antibody is not species specific and used for western blotting and immunoprecipitation. Anti-p73 antibody is against human and mouse protein, and was used for western blotting and immunoprecipitation. All antibodies used in this study are commercially available, and the validations were completed by the manufacturers. Note that full information on the approval of the study protocol must also be provided in the manuscript.

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