Reversal of spontaneous autoimmune insulitis in nonobese diabetic mice by soluble lymphotoxin receptor.

Abstract	One striking feature of spontaneous autoimmune diabetes is the prototypic formation of lymphoid follicular structures within the pancreas. Lymphotoxin (LT) has been shown to play an important role in the formation of lymphoid follicles in the spleen. To explore the potential role of LT-mediated microenvironment in the pathogenesis of insulin-dependent diabetes mellitus (IDDM), an LTbeta receptor-immunoglobulin fusion protein (LTbetaR-Ig) was administered to nonobese diabetic mice. Early treatment with LTbetaR-Ig prevented insulitis and IDDM, suggesting that LT plays a critical role in the insulitis development. LTbetaR-Ig treatment at a late stage of the disease also dramatically reversed insulitis and prevented diabetes. Moreover, LTbetaR-Ig treatment prevented the development of IDDM by diabetogenic T cells in an adoptive transfer model. Thus, LTbetaR-Ig can disassemble the well established lymphoid microenvironment in the islets, which is required for the development and progression of IDDM.
Authors	Q Wu, B Salomon, M Chen, Y Wang, L M Hoffman, J A Bluestone, Y X Fu
Journal	The Journal of experimental medicine (J Exp Med) Vol. 193 Issue 11 Pg. 1327-32 (Jun 04 2001) ISSN: 0022-1007 [Print] United States
PMID	11390440 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Cell Adhesion Molecules Immunoglobulins Ltbr protein, mouse Lymphotoxin beta Receptor Madcam1 protein, mouse Membrane Proteins Mucoproteins Receptors, Tumor Necrosis Factor Tnfsf14 protein, mouse Tumor Necrosis Factor Ligand Superfamily Member 14 Tumor Necrosis Factor-alpha
Topics	Animals Cell Adhesion Molecules Diabetes Mellitus, Type 1 (prevention & control) Female Immunoglobulins (physiology) Islets of Langerhans (pathology) Lymphotoxin beta Receptor Membrane Proteins (physiology) Mice Mice, Inbred NOD Mucoproteins (physiology) Receptors, Tumor Necrosis Factor (physiology) Tumor Necrosis Factor Ligand Superfamily Member 14 Tumor Necrosis Factor-alpha (physiology)

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