Cellular and Molecular Mechanisms of Intestinal Fibrosis

Intestinal fibrosis associated stricture is a common complication of inflammatory bowel disease usually requiring endoscopic or surgical intervention. Effective anti-fibrotic agents aiming to control or reverse intestinal fibrosis are still unavailable. Thus, clarifying the mechanism underpinning intestinal fibrosis is imperative. Fibrosis is characterized by an excessive accumulation of extracellular matrix (ECM) proteins at the injured sites. Multiple cellular types are implicated in fibrosis development. Among these cells, mesenchymal cells are major compartments that are activated and then enhance the production of ECM. Additionally, immune cells contribute to the persistent activation of mesenchymal cells and perpetuation of inflammation. Molecules are messengers of crosstalk between these cellular compartments. Although inflammation is necessary for fibrosis development, purely controlling intestinal inflammation cannot halt the development of fibrosis, suggesting that chronic inflammation is not the unique contributor to fibrogenesis. Several inflammation-independent mechanisms including gut microbiota, creeping fat, ECM interaction, and metabolic reprogramming are involved in the pathogenesis of fibrosis. In the past decades, substantial progress has been made in elucidating the cellular and molecular mechanisms of intestinal fibrosis. Here, we summarized new discoveries and advances of cellular components and major molecular mediators that are associated with intestinal fibrosis, aiming to provide a basis for exploring effective anti-fibrotic therapies in this field.

Selectively increased expression and functions of chemokine receptor CCR9 on CD4+ T cells from patients with T-cell lineage acute lymphocytic leukemia.

In a total of 38 typical T-cell lineage acute lymphocytic leukemia (T-ALL) and T-cell lineage chronic lymphocytic leukemia (T-CLL) cases investigated, we found that CC chemokine receptor CCR9 was selectively and frequently expressed on T-ALL CD4+ T cells, was moderately expressed on T-CLL CD4+ T cells, and was rarely expressed on normal CD4+ T cells. These findings were demonstrated at protein and mRNA levels using flow cytometry and real-time quantitative reverse transcription-PCR technique and were verified by digital confocal microscopy and Northern blotting. Thymus-expressed chemokine, a ligand for CCR9, selectively induced T-ALL CD4+ T-cell chemotaxis and adhesion. Interleukin (IL)-2 and IL-4, together, down-regulated the expression and functions of CCR9 in T-ALL CD4+ T cells including chemotaxis and adhesion. It was also demonstrated that IL-2 and IL-4, together, internalized CCR9 on T-ALL CD4+ T cells and subsequently inhibited functions of CCR9 in these cells. Thymus-expressed chemokine mRNA was highly expressed in CD4+ T cells, involving lymph node and skin in T-ALL patients, and was expressed at moderate levels in lymph node and skin tissues in T-CLL patients. Our findings may provide new clues to understanding various aspects of T-ALL CD4+ T cells, such as functional expression of CCR9-thymus-expressed chemokine receptor-ligand pairs as well as the effects of IL-2 and IL-4, which may be especially important in cytokine/chemokine environment for the pathophysiological events of T-ALL CD4+ T-cell trafficking.

A cross-sectional study on the correlation between MRI signal for IPFP and knee osteoarthritis / 中南大学学报(医学版)

Objective:To investigate the correlation between MRI signal for infrapatellar fat pad (IPFP) and pathological changes in knee osteoarthritis (KOA),and to analyze the role of IPFP in the development of knee osteoarthritis.Methods:A total of 114 subjects (without special knee disease) were enrolled for this study.The intensity of MRI signal for IPFP was determined by fat-suppressed proton-density-weighted turbospin-echo magnetic resonance imaging.Based on the cartilage defects and osteophytes of knee joint,the subjects were divided into a KOA group and a control group.The difference of MRI signal for IPFP between two groups was analyzed.Results:After excluding the potential confounders of age,gender and BMI,the intensity of MRI signal for IPFP was positively correlated with defections in patellar,medial femur,lateral tibial or knee joint (OR 1.333 to 2.168,P 0.006 to 0.023);the intensity of MRI signal for IPFP was also positively correlated with osteophytes in patellar,medial femur,lateral tibial or knee joint (OR 1.309 tol.781,P 0.004 to 0.046);the intensity of MR/signal for IPFP in the KOA group was significantly higher than that in the control group (P=0.028).Conclusion:The increase in the density of MRI signal for IPFP is an imaging manifestation for knee degeneration.IPFP inflammation and endocrine abnormalities may play an important role in KOA.