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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 Shi, and
David J Field, and
Kyung-ae Ko, and
Sara Ture, and
Kalyan Srivastava, and
Scott Levy, and
M Anna Kowalska, and
Mortimer Poncz, and
Deborah J Fowell, and
Craig N Morrell
February 2015,
Scandinavian journal of immunology,
Guanfang Shi, and
David J Field, and
Kyung-ae Ko, and
Sara Ture, and
Kalyan Srivastava, and
Scott Levy, and
M Anna Kowalska, and
Mortimer Poncz, and
Deborah J Fowell, and
Craig N Morrell
January 2011,
Mediators of inflammation,
Guanfang Shi, and
David J Field, and
Kyung-ae Ko, and
Sara Ture, and
Kalyan Srivastava, and
Scott Levy, and
M Anna Kowalska, and
Mortimer Poncz, and
Deborah J Fowell, and
Craig N Morrell
March 2013,
Immunobiology,
Guanfang Shi, and
David J Field, and
Kyung-ae Ko, and
Sara Ture, and
Kalyan Srivastava, and
Scott Levy, and
M Anna Kowalska, and
Mortimer Poncz, and
Deborah J Fowell, and
Craig N Morrell
June 2011,
The surgeon : journal of the Royal Colleges of Surgeons of Edinburgh and Ireland,
Guanfang Shi, and
David J Field, and
Kyung-ae Ko, and
Sara Ture, and
Kalyan Srivastava, and
Scott Levy, and
M Anna Kowalska, and
Mortimer Poncz, and
Deborah J Fowell, and
Craig N Morrell
October 2009,
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation,
Guanfang Shi, and
David J Field, and
Kyung-ae Ko, and
Sara Ture, and
Kalyan Srivastava, and
Scott Levy, and
M Anna Kowalska, and
Mortimer Poncz, and
Deborah J Fowell, and
Craig N Morrell
December 2010,
Transplantation proceedings,
Guanfang Shi, and
David J Field, and
Kyung-ae Ko, and
Sara Ture, and
Kalyan Srivastava, and
Scott Levy, and
M Anna Kowalska, and
Mortimer Poncz, and
Deborah J Fowell, and
Craig N Morrell
December 2008,
The Journal of experimental medicine,
Guanfang Shi, and
David J Field, and
Kyung-ae Ko, and
Sara Ture, and
Kalyan Srivastava, and
Scott Levy, and
M Anna Kowalska, and
Mortimer Poncz, and
Deborah J Fowell, and
Craig N Morrell
October 2002,
Circulation,
Guanfang Shi, and
David J Field, and
Kyung-ae Ko, and
Sara Ture, and
Kalyan Srivastava, and
Scott Levy, and
M Anna Kowalska, and
Mortimer Poncz, and
Deborah J Fowell, and
Craig N Morrell
July 1974,
Transplantation,
Guanfang Shi, and
David J Field, and
Kyung-ae Ko, and
Sara Ture, and
Kalyan Srivastava, and
Scott Levy, and
M Anna Kowalska, and
Mortimer Poncz, and
Deborah J Fowell, and
Craig N Morrell
January 1991,
Journal of lipid mediators,
