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FTY720 ameliorates GvHD by blocking T lymphocyte migration to target organs and by skin fibrosis inhibition.

FTY720 ameliorates GvHD by blocking T lymphocyte migration to target organs and by skin fibrosis inhibition.

Authors :
Ryu, Jaeyoon
Jhun, Jooyeon
Park, Min-Jung
Baek, Jin-ah
Kim, Se-Young
Cho, Keun-Hyung
Choi, Jeong-Won
Park, Sung-Hwan
Choi, Jong Young
Cho, Mi-La
Source :
Journal of Translational Medicine; 6/6/2020, Vol. 18 Issue 1, p1-13, 13p
Publication Year :
2020

Abstract

<bold>Background: </bold>Fibrosis is the formation of excess connective tissue in an organ or tissue during a reparative or reactive process. Graft-versus-host disease (GvHD) is a medical complication of allogeneic tissue transplantation with transplanted donor T cell-mediated inflammatory response; it is characterized by a severe immune response with fibrosis in the final stage of the inflammatory process. T helper 17 cells play a critical role in the pathogenesis of GvHD. Fingolimod (FTY720), an analogue of sphingosine-1-phosphate (S1P), is an effective immunosuppressive agent in experimental transplantation models.<bold>Methods: </bold>In this study, we evaluated the effects of FTY720 as a treatment for an animal GvHD model with inflammation and fibrosis. The splenocytes, lymph nodes, blood, tissues from Syngeneic mice and GvHD-induced mice treated vehicle or FTY720 were compared using flow cytometry, hematological analyses, histologic analyses.<bold>Results: </bold>FTY720 reduced clinical scores based on the following five clinical parameters: weight loss, posture, activity, fur texture, and skin integrity. FACS data showed that T lymphocyte numbers increased in mesenteric lymph nodes and decreased in splenocytes of FTY720-treated mice. Tissue analysis showed that FTY720 reduced skin, intestinal inflammation, and fibrotic markers. FTY720 dramatically decreased α-smooth muscle actin, connective tissue growth factor, and fibronectin protein levels in keloid skin fibroblasts.<bold>Conclusions: </bold>Thus, FTY720 suppressed migration of pathogenic T cells to target organs, reducing inflammation. FTY720 also inhibited fibrogenesis marker expression in vitro and in vivo. Together, these results suggest that FTY720 prevents GvHD progression via immunosuppression of TH17 and simultaneously acts an anti-fibrotic agent. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14795876
Volume :
18
Issue :
1
Database :
Complementary Index
Journal :
Journal of Translational Medicine
Publication Type :
Academic Journal
Accession number :
143632442
Full Text :
https://doi.org/10.1186/s12967-020-02386-w