Role of mast cells in fibrosis of classical Hodgkin lymphoma

Abstract

The underlying mechanism of fibrosis in classical Hodgkin lymphoma (CHL) remains uncertain. This study aimed to investigate the association of fibrosis in the lymph nodes of patients with CHL through histological examination of the expression of cytokines associated with fibrosis and mast cell proliferation. Additionally, we sought to determine the degree of mast cell infiltration in a nodular sclerosis subtype of CHL (NSCHL) compared with that in non-NSCHL. We analyzed lymph nodes from 22 patients with CHL, of which eight were of the NSCHL and 14 of the non-NSCHL subtype, using immunohistochemical staining of forkhead box P3 (FOXP3), transforming growth factor (TGF)-β, interleukin (IL)-3, IL-13, and stem cell factor (SCF). Mast cells were positive for TGF-β and IL-13, and FOXP3-positive cells were negative for TGF-β. Only the expression of IL-13 in Hodgkin and Reed-Sternberg (HRS) cells was significantly more frequently observed in NSCHL than that in non-NSCHL (P = 0.0028) and was associated with a higher rate of fibrosis (P = 0.0097). The number of mast cells was significantly higher in NSCHL than that in non-NSCHL (P = 0.0001). A significantly positive correlation was observed between the rate of fibrosis and the number of mast cells (correlation coefficient, 0.8524; 95% CI, 0.6725-0.9372) (P <0.0001). The number of mast cells was significantly higher in the group with IL-13-positive HRS cells than that in the group with IL-13-negative HRS cells (P = 0.0157). Based on these findings, we hypothesize that IL-13 production by HRS cells may lead to fibrosis, and furthermore, promote mast cell proliferation and infiltration. This in turn might further produce the fibrotic cytokines IL-13 and TGF-β, resulting in fibrosis typical of NSCHL.

High CD206 levels in Hodgkin lymphoma‐educated macrophages are linked to matrix‐remodeling and lymphoma dissemination

“…Of note, L428 cells are derived from NSCHL. The observed capacity of L428-CM to induce a specific Mφ subtype with high CD206 expression and collagen uptake supports the hypothesis of tissue remodeling by the interaction of lymphoma cells with stromal cells, and adds an additional element to the previously observed mast cell infiltration and fibrosis in HL (Nakayama et al, 2016). It has to be mentioned that C-type lectins facilitate the endocytosis of particular antigen types for cross-presentation, but whether antigen uptake by the C-type lectins will result in immunogenic or tolerogenic cytotoxic T-cell priming remains to be studied (Allen and R€ uckerl, 2017).…”

“…This suggests that these M2-like Mφ play a specific CD206-mediated role in lymphoma tissue reorganization. Matrix remodeling is a common process in tumor progression, and the tumor stroma is characterized by profound proteolytic degradation (Cox and Erler, 2011;Nakayama et al, 2016;Tataroglu et al, 2007). The most striking feature of the nodular sclerosis subtype of classical HL (NSCHL) is the presence of ECM deposits.…”

The Role of Mast Cells in Alzheimer’s Disease

“…Mast cells, first described in 1876 by Paul Ehrlich, are hematopoietically-derived immune cells, which are commonly found adjacent to blood vessels in the lamina propria of airway mucosa and produce pathophysiological changes in various organs, leading to the development of different inflammatory disorders [18,19] (Fig. 1).…”

Neuroendocrinology of mast cells: Challenges and controversies

“…In fact, targeting MC has been proposed as way to treat endometriosis . Mast cells have also been implicated in fibrosis, whether it is present in endometriosis or in Hodgkin's lymphoma …”