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Gene array analysis of a rat model of liver transplant tolerance identifies increased complement C3 and the STAT‐1/IRF‐1 pathway during tolerance induction
Author(s) -
Cordoba Shaun P.,
Wang Chuanmin,
Williams Rohan,
Li Jian,
Smit Lynn,
Sharland Alexandra,
Allen Richard,
McCaughan Geoffrey,
Bishop Alex
Publication year - 2006
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.20637
Subject(s) - medicine , liver transplantation , microarray , immune system , immune tolerance , stat , immunology , complement system , gene , microarray analysis techniques , transplantation , gene expression , biology , genetics , stat3
This study aimed to define the molecular mechanism during induction of spontaneous liver transplant tolerance using microarrays and to focus on molecular pathways associated with tolerance by meta‐analysis with published studies. The differences in the early immune response between PVG to DA liver transplant recipients that are spontaneously tolerant (TOL) and PVG to Lewis liver transplants that reject (REJ) were examined. Spleens from TOL and REJ on days 1 and 3 were compared by 2 color microarray. Forty‐six of 199 genes differentially expressed between TOL and REJ had an immunological function. More immune genes were increased in TOL vs. REJ on day 1, including STAT‐1, IRF‐1 and complement C3. Differential expression of selected genes was confirmed by quantitative RT‐PCR. The results were compared to two published high‐throughput studies of rat liver transplant tolerance and showed that C3 was increased in all three models, while STAT‐1 and IRF‐1 were increased in two models. The early increases in immune genes in TOL confirmed previous reports of an active early immune response in TOL. In conclusion, the increase in STAT‐1, IRF‐1 and complement component C3 in several models of liver transplant tolerance suggests that the STAT‐1/IRF‐1 apoptotic pathway and C3 may be involved in the tolerogenic mechanism. Liver Transpl 12:636–643, 2006. © 2006 AASLD.