Regulation of fibrosis by the immune system.
Inflammation and fibrosis are two inter-related conditions with many overlapping mechanisms. Three specific cell types, macrophages, T helper cells, and myofibroblasts, each play important roles in regulating both processes. Following tissue injury, an inflammatory stimulus is often necessary to initiate tissue repair, where cytokines released from resident and infiltrating leukocytes stimulate proliferation and activation of myofibroblasts. However, in many cases this drive stimulates an inappropriate pro-fibrotic response. In addition, activated myofibroblasts can take on the role of traditional APCs, secrete pro-inflammatory cytokines, and recruit inflammatory cells to fibrotic foci, amplifying the fibrotic response in a vicious cycle. Moreover, inflammatory cells have been shown to play contradictory roles in initiation, amplification, and resolution of fibrotic disease processes. The central role of the macrophage in contributing to the fibrotic response and fibrotic resolution is only beginning to be fully appreciated. In the following review, we discuss the fibrotic disease process from the context of the immune response to injury. We review the major cellular and soluble factors controlling these responses and suggest ways in which more specific and, hopefully, more effective therapies may be derived.