IL-17A Promotes Initiation and Development of Intestinal Fibrosis Through EMT

Abstract

Our study confirmed the involvement of IL-17A in the development of intestinal fibrosis through inducing EMT.

Mechanism of fibrosis and stricture formation in Crohn's disease

“…41 At the intestinal wall level, strictured mucosa ( Figure 4B: top) displays increased IL-1β 11 and IL17A. 40 Similar to the mucosa, deeper layers (defined as below muscularis mucosa) ( Figure 4B: bottom) also have increased IL-1β and IL17A, among others, 11,42 and secrete more collagen. 11,42,43 IL-17 may have a role in stricture development, and a recent review summarized the potential for Th17/IL-17 involvement in intestinal fibrosis.…”

“…This is based on observations that strictures show alterations in EMT-associated markers. 21,25,40,64 For example, several papers describe lower expression of epithelial cell markers (and/or increased extra-epithelial staining of such a marker) in stricture mucosa concomitant with increases in markers for mesenchymal cells or EMT onset. However, the contribution of EMT to the population of myofibroblasts in other fibrotic diseases has been questioned.…”

Peripheral Blood Inflammatory Markers and Crohn’s Disease: Lymphocytes Counts Could Predict Stricture Lesions 

“…IL-17A is a proinfammatory cytokine that is mainly produced and secreted by Th17 cells. Recently, IL-17A has been shown to be involved in the development of intestinal brosis by inducing epithelial-mesenchymal transition [17]. Consequently, Th17 cells are related to intestinal in ammation and brosis.…”

Hydrogen inhalation attenuated bleomycin‐induced pulmonary fibrosis by inhibiting transforming growth factor‐β1 and relevant oxidative stress and epithelial‐to‐mesenchymal transition

“…Recently, EMT was reported to be associated with tissue fibrosis by increasing the deposition of ECM (Liu et al., ; Zhang et al., ). TGF‐β1 upregulation leads to an increase in the expression of fibrosis‐associated genes ( α‐SMA and COL1A1 ), collagen production and ECM deposition in fibrotic tissue.…”

“…This means that TGF-1 may regulate oxidative stress, which occurs during the process of tissue repair/remodelling and fibrosis (Babalola, Mamalis, Lev-Tov, & Jagdeo, 2014; Barnes & Gorin 2011;Bataller et al, 2003), to result in tissue fibrosis. Recently, epithelial-to-mesenchymal transition (EMT) was reported to be associated with tissue fibrosis by driving the production of numerous ECM proteins (Liu et al, 2017a;Zhang et al, 2018). TNF-, an important pro-inflammatory factor during chronic tissue injury and inflammation, can stimulate uncontrolled ECM protein deposition, ultimately resulting in fibrosis and organ failure (Thakur, Pritchard, McMullen, & Nagy, 2006).…”