Roles of islet toll-like receptors in pig to mouse islet xenotransplantation

Han Ro, Eun Won Lee, Joo Ho Hong, Kyu Hyun Han, Hye Jung Yeom, Hwa Jung Kim, Myung Gyu Kim, Hye Seung Jung, Kook Hwan Oh, Kyong Soo Park, Curie Ahn, Jaeseok Yang

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7 Citations (Scopus)

Abstract

Although innate immunity plays important roles in xenograft rejection, there have been few studies on the role of toll-like receptors (TLRs) in xenotransplantation. Furthermore, most studies focused on the recipient's TLRs. Therefore, we investigated whether TLRs in porcine islets can contribute to islet xenograft rejection. Adult porcine islets were isolated and stimulated by polyinosinic/polycytidylic acid (poly I:C) or lipopolysaccharide (LPS). Both poly I:C and LPS stimulation in porcine islets induced expression of chemokines (RANTES, MCP-1, IP-10, and IL-8), cytokines (IL-6 and type I interferons), and adhesion molecules (VCAM-1 and ICAM-1). Porcine islet supernatants stimulated by TLR agonists induced chemotaxis of human leukocytes. They also induced procoagulant activation (tissue factor and fgl-2). However, TLR stimulation did not influence insulin secretion. When porcine MyD88 was knocked down using shRNA lentivirus, TLR-mediated induction of proinflammatory mediators and procoagulants was attenuated. When LPS was injected to MyD88 or TLR4 knockout mice after porcine islet transplantation, LPS stimulation on donor islets interfered with islet xenograft tolerance induction by anti-CD154 antibodies. Inflammatory cell infiltration and expression of proinflammatory chemokines and cytokines in islet xenografts also increased. In conclusion, TLR activation in porcine islets induced both a proinflammatory and procoagulant response and thereby contributed to xenograft rejection.

Original languageEnglish
Pages (from-to)1709-1722
Number of pages14
JournalCell Transplantation
Volume22
Issue number9
DOIs
Publication statusPublished - 2013

Keywords

  • Islet transplantation
  • Rejection
  • Toll-like receptors (TLRs)
  • Xenotransplantation

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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  • Cite this

    Ro, H., Lee, E. W., Hong, J. H., Han, K. H., Yeom, H. J., Kim, H. J., Kim, M. G., Jung, H. S., Oh, K. H., Park, K. S., Ahn, C., & Yang, J. (2013). Roles of islet toll-like receptors in pig to mouse islet xenotransplantation. Cell Transplantation, 22(9), 1709-1722. https://doi.org/10.3727/096368912X657684