Transglutaminase 2 over-Expressed By Interaction of Mast Cells and Oligodendrocytes Induces Demyelination in the Experimental Autoimmune Encephalomyelitis
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Gwan Ui Hong, Young Min Ahn, MD, Jai Youl Ro, Ph.D
Rationale: Mast cells and oligodendrocytes play important roles in autoimmune diseases like multiple sclerosis. TG2 over-expressed in various inflammatory diseases has influence on the damaged axons. This study aimed to investigate whether TG2 expressed in mast cells and oligodendrocytes induces demyelination in experimental autoimmune encephalomyelitis (EAE).  

 Methods: Wild type (WT) and TG2-/- (KO) mice received MOG33-55 and PT by i.p. injection to induce EAE. Bone marrow-derived mast cells (BMMCs) were adaptively transferred to KO mice by i.v. injection before PT injection. BMMCs and mouse cerebral cortices-derived mature OLs (mOLs) were co-cultured. Demyelinated area was determined by luxol fast blue staining, expression of surface markers and death signaling molecules by western blot, co-localization of mast cells and mOLs by immunofluorescence.

 Results: KO mice reduced EAE scores, demyelinated area, mast cell numbers, expression of surface markers (CD40/CD40L) in mast cells and death signaling molecules in mOLs, co-localization of mast cells and mOLs in thalamus of EAE, whereas WT mice increased all of them in thalamus. BMMCs-transferred KO mice restored all responses versus KO mice. KO-BMMCs co-cultured with mOLs decreased [Ca2+]i level and the release of histamine, LTs and cytokines versus WT-BMMCs with mOLs. The mOLs co-cultured with KO-BMMCs reduced expression of various death signaling molecules versus mOLs with WT-BMMCs.

 Conclusions: The data suggest that mast cells- or mOLs-expressed TG2 may induce mediators′ release and apoptosis, respectively, through up-regulating expression of various stimulatory/death signaling molecules, and that substances reducing TG2 over-expressed in thalamus of EAE may contribute to protection against demyelination of EAE.