myelin-oligodendrocyte-glycoprotein-(35-55) and Colitis

The developmental programs that generate a broad repertoire of regulatory T cells (T

Topics: Animals; Autoantigens; Cell Differentiation; Colitis; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Forkhead Transcription Factors; Freund's Adjuvant; Humans; Immune Tolerance; Interleukin-2 Receptor alpha Subunit; Lymphoid Progenitor Cells; Mice; Mice, Transgenic; Mycobacterium tuberculosis; Myelin-Oligodendrocyte Glycoprotein; Peptide Fragments; Signal Transduction; Specific Pathogen-Free Organisms; T-Lymphocytes, Regulatory; Thymus Gland

Hyperactivation of the NLRP3 inflammasome contributes to the pathogenesis of multiple diseases, but the mechanisms underlying transcriptional regulation of

Topics: Animals; Antibodies, Monoclonal; Colitis; Dextran Sulfate; Encephalomyelitis, Autoimmune, Experimental; Female; HEK293 Cells; Humans; Inflammasomes; Interleukin-1beta; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Myelin-Oligodendrocyte Glycoprotein; NLR Family, Pyrin Domain-Containing 3 Protein; Peptide Fragments; RAW 264.7 Cells; Receptors, Complement; THP-1 Cells; Transcription, Genetic

Obesity is associated with numerous inflammatory conditions including atherosclerosis, autoimmune disease and cancer. Although the precise mechanisms are unknown, obesity-associated rises in TNF-alpha, IL-6 and TGF-beta are believed to contribute. Here we demonstrate that obesity selectively promotes an expansion of the Th17 T-cell sublineage, a subset with prominent pro-inflammatory roles. T-cells from diet-induced obese mice expand Th17 cell pools and produce progressively more IL-17 than lean littermates in an IL-6-dependent process. The increased Th17 bias was associated with more pronounced autoimmune disease as confirmed in two disease models, EAE and trinitrobenzene sulfonic acid colitis. In both, diet-induced obese mice developed more severe early disease and histopathology with increased IL-17(+) T-cell pools in target tissues. The well-described association of obesity with inflammatory and autoimmune disease is mechanistically linked to a Th17 bias.

Topics: Animals; Colitis; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Glycoproteins; Interleukin-17; Interleukin-6; Male; Mice; Mice, Inbred C57BL; Myelin-Oligodendrocyte Glycoprotein; Obesity; Peptide Fragments; T-Lymphocytes, Helper-Inducer; Trinitrobenzenesulfonic Acid