Abstract
Inflammatory Bowel Disease (IBD) comprises a series of chronic and relapsing intestinal diseases, with Crohn’s disease and ulcerative colitis being the most common. The abundant and uncontrolled deposition of extracellular matrix, namely fibrosis, is one of the major hallmarks of IBD and is responsible for the progressive narrowing and closure of the intestine, defined as stenosis. Although fibrosis is usually considered the product of chronic inflammation, the substantial failure of anti-inflammatory therapies to target and reduce fibrosis in IBD suggests that fibrosis might be sustained in an inflammation-independent manner. Pharmacological therapies targeting integrins have recently shown great promise in the treatment of IBD. The efficacy of these therapies mainly relies on their capacity to target the integrin-mediated recruitment and functionality of the immune cells at the damage site. However, by nature, integrins also act as mechanosensitive molecules involved in the intracellular transduction of signals and modifications originating from the extracellular matrix. Therefore, understanding integrin signaling in the context of IBD may offer important insights into mechanisms of matrix remodeling, which are uncoupled from inflammation and could underlie the onset and persistency of intestinal fibrosis. In this review, we present the currently available knowledge on the role of integrins in the etiopathogenesis of IBD, highlighting their role in the context of immune-dependent and independent mechanisms.
Highlights
Inflammatory Bowel Disease (IBD) defines a group of chronic, relapsing, and remitting enteropathies, including Crohn’s disease (CD) and Ulcerative colitis (UC) [1]
Intestinal fibrosis is a common complication in IBD and can occur in both UC and CD, it is more prevalent in CD [9]
We aim to summarize the involvement of integrins in IBDassociated intestinal fibrosis development, taking into consideration their functional role in both immune cells and other cell types, primarily fibroblasts, highly implicated in the development of fibrotic complications
Summary
Inflammatory Bowel Disease (IBD) defines a group of chronic, relapsing, and remitting enteropathies, including Crohn’s disease (CD) and Ulcerative colitis (UC) [1]. It is well known that genetic susceptibility, alteration in the gut microbiota compositions, and environmental factors are strongly involved [2] This multifactorial scenario sustains a chronic and aberrant immune response, triggering extensive intestinal tissue damage at the inflammatory site [3,4,5]. Despite the availability of these novel biological treatments, the incidence of strictures formation has not changed and requires the development of different therapeutic strategies [15] This evidence suggests that IBD and its related complications, among which fibrosis is the most debilitating, are governed by inflammation but might be sustained and perpetuated by additional inflammation-independent mechanisms which need to be understood in depth and taken into consideration to develop new therapeutic strategies able to target these stenotic complications [16]. We aim to summarize the involvement of integrins in IBDassociated intestinal fibrosis development, taking into consideration their functional role in both immune cells and other cell types, primarily fibroblasts, highly implicated in the development of fibrotic complications
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