MicroRNAs (miRNAs) participate in distinct steps of the immune response against self-tissues. Specific miRNAs are expressed by immune and tissue resident cells and repress key proteins that are involved in distinct inflammatory pathways. Consequently, miRNAs regulate autoimmune responses at distinct points. These include activation of antigen-presenting cells (APCs), antigen receptor signaling by lymphocytes, lineage skewing by effector T lymphocytes, the function of regulatory T (Treg) cells, effector cytokine production, signaling events which occur in resident tissue cells responding to inflammatory cytokines, recruitment of additional inflammatory cells through factors such as chemokines, class-switching and germinal center formation by B cells, and non-immune cell mechanisms of tissue damage. FDC, follicular dendritic cell; IFNγ, interferon-gamma; IL, interleukin; RANTES, regulated upon activation, normal T-cell expressed, and secreted; Th, T helper; TNFα, tumor necrosis factor-alpha.