ABSTRACT
Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine that is an important trigger and initiator of many allergic diseases. TSLP promotes a T-helper type 2 (Th2) cytokine response that can be pathological. A relationship is formed both at the induction phase of the Th2 response through polarization of dendritic cells to drive Th2 cell differentiation and at the effector phase of the response, by promoting the expansion of activated T cells and their secretion of Th2 cytokines and TSLP. In transgenic mice with TSLP overexpression, it has been reported that TSLP leads to the development of mixed cryoglobulinemic membranoproliferative glomerulonephritis. In addition, TSLP can play an important role in the pathogenesis of IgA nephropathy and systemic lupus erythematosus-related nephritis. From our knowledge of the role of TSLP in the kidney, further studies including the discovery of new therapies need to be considered based on the relationship between TSLP and glomerulonephritis.
Subject(s)
Animals , Mice , Cytokines , Dendritic Cells , Glomerulonephritis , Glomerulonephritis, IGA , Glomerulonephritis, Membranoproliferative , Kidney , Mice, Transgenic , Nephritis , T-Lymphocytes , Th2 CellsABSTRACT
In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.
Subject(s)
Animals , Female , Mice , Antibodies, Helminth/blood , Chemokine CCL11/biosynthesis , Cytokines/biosynthesis , Gene Expression Profiling , Immunoglobulin E/blood , Interleukin-13/metabolism , Interleukin-4/metabolism , Interleukin-5/metabolism , Interleukins/biosynthesis , Mice, Inbred C57BL , Mice, Knockout , Receptor, PAR-2/metabolism , Th2 Cells/immunology , Trichinella spiralis/immunology , Trichinellosis/immunologyABSTRACT
Objective:To investigate the expression of a new cytokine,thymic stromal lymphopoietin (TSLP) and its receptor TSLPR in the villi of human first trimester gestation.Methods:Villi were collected from women who had undergone an artificial abortion at 7-11 weeks of normal gestation.The trophoblast cells (Tros) were isolated and cultured.The total RNA was extracted using TRIzol reagent,from both villi and the Percoll-gradient-isolated Tros,then the DNA fragments of hTSLP and hTSLPR were amplificated by RT-PCR.Villous tissues were detected for TSLP by immunohistochemistry (IHC) and Western blot.Immunocytochemistry (ICC) was carried out on cultured trophoblast cells for TSLP/TSLPR expression.Levels of TSLP in the supernatants were detected by ELISA.Results:Normal villi and the cultured Tros transcript were found to express TSLP/TSLPR mRNA and secreted TSLP protein.In addition,TSLP receptor was also expressed on trophoblasts.Conclusion:Both TSLP and its receptor are expressed on villi and trophoblast cells,which suggests that TSLP plays an important role in maternal-fetal immuno-tolerance in human early pregnancy.