The immunology of fibrosis: innate and adaptive responses

Abstract

Fibrosis is an important health problem and its pathogenetic principles are still largely unknown. It can develop either spontaneously or, more frequently, as a consequence of various underlying diseases. However, irrespective of the primary cause, fibrotic tissue is always infiltrated by mononuclear immune cells. In most instances the reason for the attraction of these cells to fibrotic tissue and their proliferation remains to be determined, however their cytokine profile shows clear-cut proinflammatory and profibrotic characteristics. In this review we discuss the innate and adaptive immune reactions associated with the development of fibrosis and the molecular basis of the profibrotic mechanisms taking place in systemic sclerosis (scleroderma), arteriosclerosis and peri-silicone mammary implant fibrosis. Fibrosis: a disease with an immune-mediated etiologyFibrosis, i.e. excessive extracellular matrix (ECM) formation with proliferation and activation of myofibroblasts, is a major global health problem, but its etiology, pathogenesis, diagnosis and therapy have yet to be addressed in detail in either basic or clinical research settings. In principle, fibrosis can occur as a consequence of many different pathologic conditions (Figure 1), the most important of which arise either spontaneously, from tissue damage, inflammatory disease, in response to foreign implants, or from tumors (see Table 1).Although the pathologic processes initiating and perpetuating these processes are rather diverse, from a biochemical and pathohistological view the end stage of the development of fibrosis seems to be very stereotypic. Thus, in all cases studied the early stages of fibrotic conditions are characterized by immunologic-inflammatory hallmarks, viz. a perivascular infiltration by mononuclear cells and the subsequent imbalance of anti-and profibrotic cytokine profiles. In most of these instances, the original antigenic stimuli triggering the lymphoid infiltration have not been identified. The emphasis of this review is placed on the general role of innate and adaptive immunity, and the respective cytokines involved in the development of fibrosis.

Pulmonary arterial hypertension (ascites syndrome) in broilers: A review

“…Local pulmonary inflammatory activity is reflected by elevated circulating levels of inflammatory cytokines (IL-1, IL-6) and chemokines (IL-8) as well as C-reactive protein that may correlate with a worse clinical outcome (Dorfműller et al, 2003;Soon et al, 2010;Kherbeck et al, 2011). An autoimmune etiology of PAH is further supported by PAH development in individuals with scleroderma-like disorders with established autoimmune phenotype and the presence of antinuclear antibodies and autoantibodies directed against EC and fibroblasts (Wick et al, 2010;Kherbeck et al, 2011;Bussone et al, 2012). Moreover, PAH has been associated with a lack of CD4+ T cells, specifically T cells with a regulatory phenotype (Treg) in affected lungs that would normally function to limit vascular endothelial injury and inflammatory/autoimmune activity and hence prevent pulmonary hypertension (Tamosiuniene et al, 2011).…”

AnIn VitroAssessment of Fibroblast and Osteoblast Response to Alendronate-Modified Titanium and the Potential for Decreasing Fibrous Encapsulation

“…3 Fibrous encapsulation can develop at almost all interfaces of implanted biomaterials since it comprises overlapping stages similar to those in wound healing and tissue repair. 4 In addition, it was also reported that aggressive fibroblasts at bone surface can produce multiple cytokines to activate osteoclastogenesis, suppress osteoblast functions, and induce local inflammation, which may subsequently cause osteolysis and implant aseptic loosening. [5][6][7] Although fibrous encapsulation can impair osseointegration and the success of orthopedic implants, it receives insufficient attention in scientific and clinical research.…”

Endothelin-1 Signaling Promotes Fibrosis In Vitro in a Bronchopulmonary Dysplasia Model by Activating the Extrinsic Coagulation Cascade

“…Moreover, thrombin has been linked to the production of procollagen (11) and the expression of connective tissue growth factor (CTGF), a crucial fibrotic factor, in lung fibroblasts via the proteaseactivated receptor 1 (PAR-1) (11,12). One of the main cell types that contribute to fibrosis via collagen production is myofibroblasts (16,17). Although they originate from the differentiation of several cell populations in different tissues, they share a common function (18), producing profibrotic mediators.…”