Chronic rejection: a significant role for Th17-mediated autoimmune responses to self-antigens

Abstract

Despite progress in the field of organ transplantation for improvement in graft survival and function, long-term graft function is still limited by the development of chronic allograft rejection. Various immune-mediated and nonimmune-mediated processes have been postulated in the pathogenesis of chronic rejection. In this review, the authors discuss the important role of alloimmune responses to donor-specific antigens and autoimmune responses to tissue restricted self-antigens in the immunopathogenesis of chronic rejection following solid organ transplantation. In particular, the authors discuss the role of induction of Th17-type autoimmune responses and the crosstalk between autoimmune and alloimmune responses. These self-perpetuate each other leading to activation of profibrotic and proinflammatory cascades that ultimately result in the development of chronic rejection.

Keywords::

• alloimmunity
• autoimmunity
• chronic rejection
• Th17
• Tregs

Financial & competing interests disclosure

The work is supported by NIH grants HL056643 and HL092514, and the BJC Foundation (to T Mohanakumar). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.