Differentiating the roles of STAT5B and STAT5A in human CD4+ T cells

Jennifer A. Jenks, Scott Seki, Takahiro Kanai, Jennifer Huang, Alexander A. Morgan, Renata C. Scalco, Ruhi Nath, Robert Bucayu, Jan M. Wit, Waleed Al-Herz, Dina Ramadan, Alexander A. Jorge, Rosa Bacchetta, Vivian Hwa, Ron Rosenfeld, Kari C. Nadeau

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)227-236
Number of pages10
JournalClinical Immunology
Issue number2
Publication statusPublished - Aug 2013


  • Regulatory T cells (Treg)
  • STAT5
  • T cell development

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy


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