title: Foxp3 regulates megakaryopoiesis and platelet function.
abstract: OBJECTIVE
  Platelets are crucial for hemostasis and are vital regulators of inflammation. Foxp3 is a key transcription factor for T regulatory cell development. Humans with IPEX (immune dysregulation, polyendocrinopathy, enteropathy, x-linked) and the scurfy (Foxp3(sf)) mouse have mutations in the Foxp3 gene that lead to a host of pathologies including autoimmunity and skin diseases. Scurfy mice and some humans with IPEX are also thrombocytopenic. The purpose of this study was to determine whether the absence of functional Foxp3 leads to defects in megakaryocytes and platelets.
  
  
  RESULTS
  We discovered that human and mouse megakaryocytes express Foxp3 mRNA and protein. Using shRNA and Foxp3(sf) mice, we demonstrated that Foxp3-deficient mouse and human megakaryocyte progenitors exhibited proliferation defects. Striking platelet abnormalities were observed in both an IPEX patient and Foxp3(sf) mice. Impaired platelet spreading and release of TGF-beta and CD40 ligand (CD40L), and abnormal levels of plasma CD40L were observed in a case of IPEX syndrome. Foxp3(sf) mice were thrombocytopenic and had increased platelet volume and altered serum levels of CD40L, TXB(2), and TGF-beta.
  
  
  CONCLUSIONS
  These findings provide compelling new evidence that Foxp3 is needed for proper megakaryopoiesis and plays a role in regulating platelet function including spreading and release.
authors: Department of Environmental Medicine, University of Rochester, Rochester, NY 14642, USA.
authors: Jamie J
authors: JJ
authors: Bernard
authors: Kathryn E
authors: KE
authors: Seweryniak
authors: Anne D
authors: AD
authors: Koniski
authors: Sherry L
authors: SL
authors: Spinelli
authors: Neil
authors: N
authors: Blumberg
authors: Charles W
authors: CW
authors: Francis
authors: Mark B
authors: MB
authors: Taubman
authors: James
authors: J
authors: Palis
authors: Richard P
authors: RP
authors: Phipps
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D013045:Species Specificity; D034061:Thrombopoiesis / Q000502:physiology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D012333:RNA, Messenger