Abstract
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 language | English (US) |
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Pages (from-to) | 227-236 |
Number of pages | 10 |
Journal | Clinical Immunology |
Volume | 148 |
Issue number | 2 |
DOIs | |
State | Published - Aug 2013 |
Externally published | Yes |
Keywords
- Regulatory T cells (Treg)
- STAT5
- T cell development
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology