Distinct requirements for Stat4 and Stat6 in hematopoietic progenitor cell responses to growth factors and chemokines

Mark H. Kaplan, Hua Chen Chang, Scott Cooper, Younghee Lee, Hal E. Broxmeyer

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Hematopoietic progenitor cell (HPC) homeostasis is critical in maintaining innate immunity and healing processes. Recently, we demonstrated that Th1 cells regulate HPC homeostasis, partly based on altered homeostasis in Stat4- and Stat6-deficient mice. To explore changes in HPC responsiveness in altered T helper cell environments, we directly examined growth factor-stimulated colony formation and chemokine-induced myelosuppression of HPC in Stat4- and Stat6-deficient bone marrow cells. Stat6-deficient cells have increased responses to the synergy between granulocyte-macrophage colony-stimulating factor (GM-CSF) and steel factor (SLF), compared to wild-type and Stat4-deficient cells. Increased responses are eliminated by in vivo depletion of CD4 cells. Whereas Stat6-deficient bone marrow cells respond to chemokine-mediated myelosuppression, Stat4-deficient bone marrow cells are refractory to the suppressive effects of chemokines. Thus, T helper cell development affects HPC homeostasis through several mechanisms, including the sensitivity to growth factor stimulation and chemokine suppression of HPC colony formation. Since Stat4 and Stat6 regulate opposing programs of T helper differentiation, there are distinct requirements for Stat4 and Stat6 in regulation of growth factor and chemokine responses of HPC.

Original languageEnglish (US)
Pages (from-to)401-408
Number of pages8
JournalJournal of Hematotherapy and Stem Cell Research
Volume12
Issue number4
DOIs
StatePublished - Aug 1 2003

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ASJC Scopus subject areas

  • Immunology
  • Hematology

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