Immune System Diseases Commons^™

Epigenetic Silencing Of Socs3 Expression Contributes To Fibrosis In Crohn’S Disease, Emily T. Marshall, Chao Li, John K. Kuemmerle

MD Student Summer Research Fellowship Program Posters

Identified risk polymorphisms affecting the Jak-STAT3 pathway in patients with Crohn’s disease could affect TGF-β1 and collagen I expression and in the pathway’s negative regulator, SOCS3. Genetic factors, however, account for only ~25% of disease. Epigenetic events also shape gene expression. Recent experiments showed that autocrine IL-6 production in mesenchymal cells, subepithelial myofibroblasts (SEMF) and muscle cells, of patients with fibrostenotic Crohn’s disease causes sustained Jak-STAT3 activity, excess TGF-β1 and Collagen I production and fibrosis. SOCS3 paradoxically decreased in these cells. We now identify epigenetic mechanisms that silence SOCS3 expression in SEMF of patients with fibrostenotic Crohn’s disease. In a …

Type 2 Immune Responses In The Context Of Helminth Infection, Asthma, Dendritic Cells, And Myeloid Derived Suppressor Cell Function, Sheela Ruby Damle

Theses and Dissertations

Type 2 (T_H2) immune responses evolved to respond to helminth parasite infections by the production of T_H2 cytokines, which stimulate anti-helminth immunity. Macrophage migration inhibitor factor (MIF) is a pleiotropic cytokine, which is produced by many cell types. We demonstrate that mice deficient in MIF have enhanced clearance of a helminth parasite. MIF deficiency in CD4⁺ T cells was found to be the most important for mediating parasite clearance. We mimicked MIF deficiency by administering an inhibitor of the MIF tautomerase activity, sulforaphane, and this also increased parasite clearance (Section I).

T_H2 immune …

Mast Cell Activation By Diverse Stimuli Can Be Suppressed By Steroid Therapy And Targeting The Fyn-Stat5b Cascade, Anuya Paranjape

Theses and Dissertations

Mast cells are critical effectors of allergic disease that can be activated by numerous stimuli. We have examined mast cell control by the inflammatory cytokine, IL-33, as well as IgG. In the first study reported here, we found that the synthetic glucocorticoid, dexamethasone, potently and rapidly suppressed IL-33-induced cytokine production from murine bone marrow–derived and peritoneal mast cells, as well as human mast cells. Dexamethasone also antagonized IL-33-mediated enhancement of IgE-induced cytokine production and migration. Although dexamethasone had no effect on IL-33-induced phosphorylation of MAP kinases or NFκB p65 subunit, it antagonized AP-1 and NFκB-mediated transcriptional activity. Finally, intraperitoneal administration …