Cutting Edge: T Cell Ig Mucin-3 Reduces Inflammatory Heart Disease by Increasing CTLA-4 during Innate Immunity

• Published in: The Journal of immunology (1950) Vol. 176; no. 11; pp. 6411 - 6415
• Main Authors: Frisancho-Kiss, Sylvia, Nyland, Jennifer F, Davis, Sarah E, Barrett, Masheka A, Gatewood, Shannon J. L, Njoku, Dolores B, Cihakova, Daniela, Silbergeld, Ellen K, Rose, Noel R, Fairweather, DeLisa
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.06.2006
• Subjects: Acute Disease; Animals; Antibodies, Blocking - administration & dosage; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigens, CD; Antigens, Differentiation - biosynthesis; Cell Movement - immunology; CTLA-4 Antigen; Down-Regulation - immunology; Enterovirus B, Human - immunology; Enterovirus Infections - immunology; Enterovirus Infections - metabolism; Enterovirus Infections - pathology; Enterovirus Infections - prevention & control; Flow Cytometry; Hepatitis A Virus Cellular Receptor 2; Immunity, Innate; Inflammation Mediators - physiology; Male; Mast Cells - immunology; Mast Cells - metabolism; Mice; Mice, Inbred BALB C; Monocytes - immunology; Monocytes - metabolism; Myocarditis - immunology; Myocarditis - metabolism; Myocarditis - pathology; Myocarditis - prevention & control; Receptors, Virus - antagonists & inhibitors; Receptors, Virus - biosynthesis; Receptors, Virus - immunology; Receptors, Virus - physiology; Signal Transduction - immunology; Th1 Cells - immunology; Th1 Cells - metabolism; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.176.11.6411

Autoimmune diseases can be reduced or even prevented if proinflammatory immune responses are appropriately down-regulated. Receptors (such as CTLA-4), cytokines (such as TGF-beta), and specialized cells (such as CD4+CD25+ T regulatory cells) work together to keep immune responses in check. T cell Ig mucin (Tim) family proteins are key regulators of inflammation, providing an inhibitory signal that dampens proinflammatory responses and thereby reducing autoimmune and allergic responses. We show in this study that reducing Tim-3 signaling during the innate immune response to viral infection in BALB/c mice reduces CD80 costimulatory molecule expression on mast cells and macrophages and reduces innate CTLA-4 levels in CD4+ T cells, resulting in decreased T regulatory cell populations and increased inflammatory heart disease. These results indicate that regulation of inflammation in the heart begins during innate immunity and that Tim-3 signaling on cells of the innate immune system critically influences regulation of the adaptive immune response.