Immune and Non-Immune Inflammatory Cells Involved in Autoimmune Fibrosis: New Discoveries

Abstract

Fibrosis is an important health problem and its pathogenetic activation is still largely unknown. It can develop either spontaneously or, more frequently, as a consequence of various underlying diseases, such as chronic inflammatory autoimmune diseases. Fibrotic tissue is always characterized by mononuclear immune cells infiltration. The cytokine profile of these cells shows clear proinflammatory and profibrotic characteristics. Furthermore, the production of inflammatory mediators by non-immune cells, in response to several stimuli, can be involved in the fibrotic process. It is now established that defects in the abilities of non-immune cells to mediate immune regulation may be involved in the pathogenicity of a series of inflammatory diseases. The convergence of several, not yet well identified, factors results in the aberrant activation of non-immune cells, such as epithelial cells, endothelial cells, and fibroblasts, that, by producing pro-inflammatory molecules, exacerbate the inflammatory condition leading to the excessive and chaotic secretion of extracellular matrix proteins. However, the precise cellular mechanisms involved in this process have not yet been fully elucidated. In this review, we explore the latest discoveries on the mechanisms that initiate and perpetuate the vicious circle of abnormal communications between immune and non-immune cells, responsible for fibrotic evolution of inflammatory autoimmune diseases.

Interleukin-23 Involved in Fibrotic Autoimmune Diseases: New Discoveries

“…The induction of CCR2 expression that regulates monocyte chemotaxis and the increased fibroblast migration suggest a direct role for IL-23 in fibrotic lung disease associated with a Th17-biased immune response [63]. In this context, a process strictly correlated with fibrotic evolution [2,3] plays a role, represented by EMT, which seems to be activated in the lung by chronic inflammatory stimuli and tissue damage. The EMT process creates an environment that facilitates fibrosis when alveolar epithelial cells are injured.…”

“…Sjögren's syndrome (SS) is an autoimmune disease characterized by a chronic inflammatory response that causes a morphological and functional alteration of the exocrine glands, in particular the salivary and lacrimal glands, and this seriously compromises the quality of life of these patients [2,3]. "Primary" SS is defined as a standalone entity occurring in the absence of another systemic autoimmune disease, whereas "secondary" disease is associated with the presence of other autoimmune conditions, such as RA, SLE, or systemic sclerosis (SSc).…”

“…Therefore, therapeutic strategies directed against the TLR/IL-17 pathway might be valid candidates for the treatment of SS [75]. In recent years, a thriving research sector has demonstrated that SS is often accompanied by fibrotic phenomena affecting the salivary glands mediated by the activation of the EMT program, triggered by the chronic inflammation that characterizes the disease [2,3]. Therefore, based on the attribution of an important role for IL-23 in the exacerbation of the disease, there are all the premises to identify a correlation between IL-23 expression, chronic inflammation, and fibrosis in SS.…”

“…Multiple autoimmune diseases are a group of clinically heterogeneous conditions that show common inflammatory signaling pathways arising from aberrant immune responses [1]. Some of these disorders are characterized by intense and severe fibrotic processes as the result of a complex interplay between different immune cell types following persistent inflammatory activity [2,3]. Autoimmune diseases, traditionally characterized by chronic inflammation, present tissue damage that often evolves towards fibrosis.…”

“…The fibrotic evolution of autoimmune diseases presents an excessive release of pro-fibrotic factors as a result of the activation of molecular cascades depending on chronic inflammation. In recent years, researchers' efforts have focused on identifying molecular bridges that can connect the various fibrotic pathways identified so far [2,3]. Several cytokines have been well studied for their ability to generate inflammatory loops through positive feedback mechanisms [4].…”