Intestinal
fibrosis is a late-stage phenotype of
inflammatory bowel disease (IBD), which underlies most of the long-term complications and surgical interventions in patients, particularly those with
Crohn's disease. Despite these issues, antifibrotic
therapies are still scarce, mainly due to the current lack of understanding concerning the pathogenetic mechanisms that mediate fibrogenesis in patients with chronic intestinal
inflammation. In the current review, we summarize recent evidence regarding the cellular and molecular factors of innate and adaptive immunity that are considered critical for the initiation and amplification of extracellular matrix deposition and
stricture formation. We focus on the role of
cytokines by dissecting the pro- vs antifibrotic components of the immune response, while taking into consideration their temporal association to the progressive stages of the natural history of IBD. We critically present evidence from animal models of intestinal
fibrosis and analyze
inflammation-
fibrosis interactions that occur under such experimental scenarios. In addition, we comment on recent findings from large-scale, single-cell profiling of
fibrosis-relevant populations in IBD patients. Based on such evidence, we propose future potential targets for antifibrotic
therapies to treat patients with IBD.