Platelet factor 4 limits Th17 differentiation and cardiac allograft rejection.
Th cells are the major effector cells in transplant rejection and can be divided into Th1, Th2, Th17, and Treg subsets. Th differentiation is controlled by transcription factor expression, which is driven by positive and negative cytokine and chemokine stimuli at the time of T cell activation. Here we discovered that chemokine platelet factor 4 (PF4) is a negative regulator of Th17 differentiation. PF4-deficient and platelet-deficient mice had exaggerated immune responses to cardiac transplantation, including increased numbers of infiltrating Th17 cells and increased plasma IL-17. Although PF4 has been described as a platelet-specific molecule, we found that activated T cells also express PF4. Furthermore, bone marrow transplantation experiments revealed that T cell-derived PF4 contributes to a restriction in Th17 differentiation. Taken together, the results of this study demonstrate that PF4 is a key regulator of Th cell development that is necessary to limit Th17 differentiation. These data likely will impact our understanding of platelet-dependent regulation of T cell development, which is important in many diseases, in addition to transplantation.
Guanfang
G
Shi
David J
DJ
Field
Kyung-ae
KA
Ko
Sara
S
Ture
Kalyan
K
Srivastava
Scott
S
Levy
M Anna
MA
Kowalska
Mortimer
M
Poncz
Deborah J
DJ
Fowell
Craig N
CN
Morrell
D000818:Animals; D001792:Blood Platelets / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000378:metabolism*; D016027:Heart Transplantation; D006706:Homeostasis; D006801:Humans; D020381:Interleukin-17 / Q000097:blood; D019169:Jurkat Cells; D051379:Mice; D008822:Mice, Transgenic; D010978:Platelet Factor 4 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology*; D013997:Time Factors; D019076:Transgenes
D020381:Interleukin-17; D011994:Recombinant Proteins; D010978:Platelet Factor 4