Th1 cells regulate hematopoietic progenitor cell homeostasis by production of oncostatin M.
Regulation of hematopoietic progenitor cell homeostasis is crucial for maintenance of innate immunity and the ability of the body to respond to injury and infection. In this report, we demonstrate that progenitor cell numbers and cycling status in vivo are dramatically increased in mice deficient in Stat6 and decreased in mice deficient in Stat4, targeted mutations which also alter T helper cell polarization. Experiments using mice that have T cell restricted transgenic expression of Stat4 or Stat6 or have been in vivo depleted of T cell subsets demonstrate that CD4(+) T cells regulate progenitor cell activity. Injection of the Th1 cytokine Oncostatin M but not other cytokines into Stat4-deficient mice recovers progenitor cell activity to wild-type levels. Thus, T helper cells actively regulate hematopoietic progenitor cell homeostasis.
Broxmeyer
Hal E
HE
Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA. mkaplan2@iupui.edu
Bruns
Heather A
HA
Zhang
Shangming
S
Cooper
Scott
S
Hangoc
Giao
G
McKenzie
Andrew N J
AN
Dent
Alexander L
AL
Schindler
Ulrike
U
Naeger
Lisa K
LK
Hoey
Timothy
T
Kaplan
Mark H
MH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism*; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D018417:Th1 Cells / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*
D004268:DNA-Binding Proteins; C508351:OSM protein, human; C508352:Osm protein, mouse; D010455:Peptides; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C494091:Stat4 protein, mouse; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D053683:Oncostatin M