Open AccessNovel Sphingosine-1-Phosphate Receptor Modulator KRP203 Combined With Locally Delivered Regulatory T Cells Induces Permanent Acceptance of Pancreatic Islet Allografts
Author(s) -
Mithun Khattar,
Ronghai Deng,
Barry D. Kahan,
Paul M. Schroder,
Tammy Phan,
Lynne P. Rutzky,
Stanislaw M. Stepkowski
Publication year - 2013
Publication title -
transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/tp.0b013e3182842396
Subject(s) - islet , foxp3 , immunosuppression , medicine , transplantation , ratón , sphingosine 1 phosphate , pharmacology , immunology , receptor , endocrinology , sphingosine , immune system , diabetes mellitus
KRP203, a structural FTY720 analogue, has 5-fold greater selectivity for binding to sphingosine-1-phosphate receptor (S1PR) 1 (S1PR(1)) versus S1PR3 and 100-fold greater selectivity over S1PR(2) and S1PR(5). Although the immunoregulatory effects of FTY720 have been tested in clinical and experimental research, the therapeutic efficacy of KRP203 in allograft models remains elusive. In this study, we investigated the potential of KRP203 alone and in combination with intragraft injection of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) to induce islet allograft tolerance.