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  • Differentiating the roles of STAT5B and STAT5A in human CD4(+) T cells CLINICAL IMMUNOLOGY Jenks, J. A., Seki, S., Kanai, T., Huang, J., Morgan, A. A., Scalco, R. C., Nath, R., Bucayu, R., Wit, J. M., Al-Herz, W., Ramadan, D., Jorge, A. A., Bacchetta, R., Hwa, V., Rosenfeld, R., Nadeau, K. C. 2013; 148 (2): 227-236


    STAT5A and STAT5B are highly homologous proteins whose distinctive roles in human immunity remain unclear. However, STAT5A sufficiency cannot compensate for STAT5B defects, and human STAT5B deficiency, a rare autosomal recessive primary immunodeficiency, is characterized by chronic lung disease, growth failure and autoimmunity associated with regulatory T cell (Treg) reduction. We therefore hypothesized that STAT5A and STAT5B play unique roles in CD4(+) T cells. Upon knocking down STAT5A or STAT5B in human primary T cells, we found differentially regulated expression of FOXP3 and IL-2R in STAT5B knockdown T cells and down-regulated Bcl-X only in STAT5A knockdown T cells. Functional ex vivo studies in homozygous STAT5B-deficient patients showed reduced FOXP3 expression with impaired regulatory function of STAT5B-null Treg cells, also of increased memory phenotype. These results indicate that STAT5B and STAT5A act partly as non-redundant transcription factors and that STAT5B is more critical for Treg maintenance and function in humans.

    View details for DOI 10.1016/j.clim.2013.04.014

    View details for Web of Science ID 000322101300009

    View details for PubMedID 23773921

    View details for PubMedCentralID PMC4169138

  • Stat5b (Signal Transducer and Activator of Transcription 5b), Not Stat5a, Is a Critical Modulator of Human Treg Development and Function Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) Jenks, J., Seki, S., Huang, J., Nath, R., Madmedov, M., Hwa, V., Rosenfeld, R., Nadeau, K. C. MOSBY-ELSEVIER. 2012: AB10–AB10