Mast Cell Involvement in Fibrosis in Chronic Graft-Versus-Host Disease

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host disease (GVHD), classified as either acute or chronic GVHD. While the pathology of acute GVHD is better understood, factors driving GVHD at the cellular and molecular level are less clear. Mast cells are an arm of the immune system that are known for atopic disease. However, studies have demonstrated that they can play important roles in tissue homeostasis and wound healing, and mast cell dysregulation can lead to fibrotic disease. Interestingly, in chronic GVHD, aberrant wound healing mechanisms lead to pathological fibrosis, but the cellular etiology driving this is not well-understood, although some studies have implicated mast cells. Given this novel role, we here review the literature for studies of mast cell involvement in the context of chronic GVHD. While there are few publications on this topic, the papers excellently characterized a niche for mast cells in chronic GVHD. These findings may be extended to other fibrosing diseases in order to better target mast cells or their mediators for treatment of fibrotic disease.

Anti‐KIT monoclonal antibody CDX‐0159 induces profound and durable mast cell suppression in a healthy volunteer study

“…10,12 MC activation underlies the etiology of allergic reactions and has been strongly implicated in chronic acute and pruritic conditions, neuroinflammatory disorders, pain, fibrosis, and autoimmune diseases. 5,6,[13][14][15][16][17][18][19][20][21][22] Indeed, therapies that inhibit specific MC triggers, such as anti-IgE (omalizumab) or mediators (antihistamines) have been approved by health authorities and recommended by guidelines as therapies, 23,24 although many patients have limited benefit indicating additional MC triggers or mediators are likely involved.…”

Key Genetic Components of Fibrosis in Diabetic Nephropathy: An Updated Systematic Review and Meta-Analysis

“…Based on the statistically significant results of the present systematic review and meta-analysis, it should be noted that mast cells (MCs) are implicated in many fibrotic conditions [ 47 , 48 , 49 , 50 ]. ACE , IL1B , IL-6 , and IL-10 are key mediators of MCs, and these genes have produced statistically significant results in the present systematic review and meta-analysis.…”

“…It has been also found that an increase in the number of MCs is correlated negatively with renal function [ 53 , 54 ], but is correlated positively with the extent of fibrosis [ 54 , 55 , 56 ]. One more reason for the inconsistency is the fact that MCs produce both pro-fibrotic and anti-fibrotic mediators [ 49 , 57 , 58 , 59 , 60 ].…”

Intestinal Fibrosis in Inflammatory Bowel Disease and the Prospects of Mesenchymal Stem Cell Therapy

“…Interestingly, MCs seem to show contradictory effects in different conditions from different researches. Some studies report that when fibrosis starts in the tissue, the MCs increase and are activated, as shown by degranulation and secretion of cytokines including TGFb and other tryptases, which accelerate the ECM production and promote the progression offibrosis (88). Bin Liu and colleagues also documented the elevated presence of MCs in fibrotic intestinal tissues, and MCs affected the development of fibrosis with the release of tryptase.…”