In both Crohn's disease (CD) and ulcerative colitis (UC), the gut is massively infiltrated with B cells and plasma cells, but the role of these cell types in the pathogenesis of gut tissue damage remains largely unknown. Human B cells express granzyme B (GrB) when cultured with IL-21, a cytokine overproduced in CD and UC mucosa. We therefore examined whether mucosal B cells express GrB and have cytotoxic activity in inflammatory bowel disease (IBD). GrB-expressing CD19(+) and IgA(+) cells were seen in the normal intestinal mucosa, but they were significantly more frequent in both CD and UC. In contrast, only a minority of CD19(+) and IgA(+) cells expressed perforin with no difference between IBD and controls. GrB-producing CD19(+) cells expressed CD27 and were CD38(high) and CD20 negative. CD19(+) B cells from IBD patients induced HCT-116 cell death. IL-21 enhanced GrB expression in control CD19(+) B cells and increased their cytotoxic activity. These data indicate that IBD-related inflammation is marked by mucosal accumulation of cytotoxic, GrB-expressing CD19(+) and IgA(+) cells, suggesting a role for these cells in IBD-associated epithelial damage.

Cupi, M., Sarra, M., Marafini, I., Monteleone, I., Franzè, E., Ortenzi, A., et al. (2014). Plasma cells in the mucosa of patients with inflammatory bowel disease produce granzyme B and possess cytotoxic activities. JOURNAL OF IMMUNOLOGY, 192(12), 6083-6091 [10.4049/jimmunol.1302238].

Plasma cells in the mucosa of patients with inflammatory bowel disease produce granzyme B and possess cytotoxic activities

MONTELEONE, IVAN;ORTENZI, ANGELA;COLANTONI, ALFREDO;SICA, GIUSEPPE;SILERI, PIERPAOLO;PALLONE, FRANCESCO;MONTELEONE, GIOVANNI
2014-06-15

Abstract

In both Crohn's disease (CD) and ulcerative colitis (UC), the gut is massively infiltrated with B cells and plasma cells, but the role of these cell types in the pathogenesis of gut tissue damage remains largely unknown. Human B cells express granzyme B (GrB) when cultured with IL-21, a cytokine overproduced in CD and UC mucosa. We therefore examined whether mucosal B cells express GrB and have cytotoxic activity in inflammatory bowel disease (IBD). GrB-expressing CD19(+) and IgA(+) cells were seen in the normal intestinal mucosa, but they were significantly more frequent in both CD and UC. In contrast, only a minority of CD19(+) and IgA(+) cells expressed perforin with no difference between IBD and controls. GrB-producing CD19(+) cells expressed CD27 and were CD38(high) and CD20 negative. CD19(+) B cells from IBD patients induced HCT-116 cell death. IL-21 enhanced GrB expression in control CD19(+) B cells and increased their cytotoxic activity. These data indicate that IBD-related inflammation is marked by mucosal accumulation of cytotoxic, GrB-expressing CD19(+) and IgA(+) cells, suggesting a role for these cells in IBD-associated epithelial damage.
15-giu-2014
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/12 - GASTROENTEROLOGIA
English
Cupi, M., Sarra, M., Marafini, I., Monteleone, I., Franzè, E., Ortenzi, A., et al. (2014). Plasma cells in the mucosa of patients with inflammatory bowel disease produce granzyme B and possess cytotoxic activities. JOURNAL OF IMMUNOLOGY, 192(12), 6083-6091 [10.4049/jimmunol.1302238].
Cupi, M; Sarra, M; Marafini, I; Monteleone, I; Franzè, E; Ortenzi, A; Colantoni, A; Sica, G; Sileri, P; Rosado, M; Carsetti, R; Macdonald, T; Pallone...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/97035
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