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, Ronald (Ron) Rosenfeld, Kari C. Nadeau

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)227-236
Number of pages10
JournalClinical Immunology
Volume148
Issue number2
DOIs
StatePublished - Aug 2013

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T-Lymphocytes
Regulatory T-Lymphocytes
Null Lymphocytes
Autoimmunity
Lung Diseases
Immunity
Chronic Disease
Transcription Factors
Maintenance
Phenotype
Growth
Proteins

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Jenks, J. A., Seki, S., Kanai, T., Huang, J., Morgan, A. A., Scalco, R. C., ... Nadeau, K. C. (2013). Differentiating the roles of STAT5B and STAT5A in human CD4+ T cells. Clinical Immunology, 148(2), 227-236. https://doi.org/10.1016/j.clim.2013.04.014

Differentiating the roles of STAT5B and STAT5A in human CD4+ T cells. / Jenks, Jennifer A.; Seki, Scott; Kanai, Takahiro; Huang, Jennifer; Morgan, Alexander A.; Scalco, Renata C.; Nath, Ruhi; Bucayu, Robert; Wit, Jan M.; Al-Herz, Waleed; Ramadan, Dina; Jorge, Alexander A.; Bacchetta, Rosa; Hwa, Vivian; Rosenfeld, Ronald (Ron); Nadeau, Kari C.

In: Clinical Immunology, Vol. 148, No. 2, 08.2013, p. 227-236.

Research output: Contribution to journalArticle

Jenks, JA, Seki, S, Kanai, T, Huang, J, Morgan, AA, Scalco, RC, Nath, R, Bucayu, R, Wit, JM, Al-Herz, W, Ramadan, D, Jorge, AA, Bacchetta, R, Hwa, V, Rosenfeld, RR & Nadeau, KC 2013, 'Differentiating the roles of STAT5B and STAT5A in human CD4+ T cells', Clinical Immunology, vol. 148, no. 2, pp. 227-236. https://doi.org/10.1016/j.clim.2013.04.014
Jenks JA, Seki S, Kanai T, Huang J, Morgan AA, Scalco RC et al. Differentiating the roles of STAT5B and STAT5A in human CD4+ T cells. Clinical Immunology. 2013 Aug;148(2):227-236. https://doi.org/10.1016/j.clim.2013.04.014
Jenks, Jennifer A. ; Seki, Scott ; Kanai, Takahiro ; Huang, Jennifer ; Morgan, Alexander A. ; Scalco, Renata C. ; Nath, Ruhi ; Bucayu, Robert ; Wit, Jan M. ; Al-Herz, Waleed ; Ramadan, Dina ; Jorge, Alexander A. ; Bacchetta, Rosa ; Hwa, Vivian ; Rosenfeld, Ronald (Ron) ; Nadeau, Kari C. / Differentiating the roles of STAT5B and STAT5A in human CD4+ T cells. In: Clinical Immunology. 2013 ; Vol. 148, No. 2. pp. 227-236.
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