Role of mast cells in fibrosis of classical Hodgkin lymphoma.
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.
Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan in1304@osaka-med.ac.jp.
Shoko
S
Nakayama
Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan.
Taiji
T
Yokote
Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan.
Nobuya
N
Hiraoka
Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan.
Uta
U
Nishiwaki
Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan.
Toshiaki
T
Hanafusa
Division of Mathematics, Osaka Medical College, Osaka, Japan.
Yasuichiro
Y
Nishimura
Division of Surgical Pathology, Osaka Medical College, Osaka, Japan.
Motomu
M
Tsuji
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology*; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult
C508596:IL3 protein, human; D018793:Interleukin-13; D007377:Interleukin-3; D016212:Transforming Growth Factor beta
IL-13; classical Hodgkin lymphoma; mast cell; stem cell factor; transforming growth factor (TGF)-β