| The process of autoimmune heart disease has been the subject of extensive investigation in the several decades since the definitive identification of infectious agents associated with the development of subsequent autoimmune disease. In a mouse model of virus-independent autoimmune myocarditis (EAM), we have sought to investigate the mechanisms underlying the regulation of autoimmunity by CD4+ T cell-derived cytokines, including IFNgamma, IL13, and IL17. Of the many effector mechanisms induced by these pathways, a new understanding of functional diversity among cells of the monocyte and macrophage lineages made these cells an interesting object of study---macrophages integrate signals from a variety of T cell-derived, inflammatory, and innate cytokines. We have investigated how these cytokines interact with each other, upon macrophage populations, and through trans mediators, such as GM-CSF in regulating the pathophysiologic processes underlying autoimmune myocarditis, and its eventual progression to cardiomyopathy. We have uncovered evidence that CSF regulation of the availability of macrophage precursors is a critical point of regulation in EAM, integrating multiple T cell-derived signals. |
