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

Maria Laura Cupi, Massimiliano Sarra, Irene Marafini, Ivan Monteleone, Eleonora Franzè, Angela Ortenzi, Alfredo Colantoni, Giuseppe Sica, Pierpaolo Sileri, M. Manuela Rosado, Rita Carsetti, Thomas T. Macdonald, Francesco Pallone, Giovanni Monteleone

Research output: Contribution to journalArticle

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 CD38high 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.

Original languageEnglish
Pages (from-to)6083-6091
Number of pages9
JournalJournal of Immunology
Volume192
Issue number12
DOIs
Publication statusPublished - Jun 15 2014

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Granzymes
Plasma Cells
Inflammatory Bowel Diseases
Mucous Membrane
B-Lymphocytes
Ulcerative Colitis
Crohn Disease
Immunoglobulin A
HCT116 Cells
Perforin
Intestinal Mucosa
Cell Death
Cytokines
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

Cupi, M. L., Sarra, M., Marafini, I., Monteleone, I., Franzè, E., Ortenzi, A., ... Monteleone, G. (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. https://doi.org/10.4049/jimmunol.1302238

Plasma cells in the mucosa of patients with inflammatory bowel disease produce granzyme B and possess cytotoxic activities. / Cupi, Maria Laura; Sarra, Massimiliano; Marafini, Irene; Monteleone, Ivan; Franzè, Eleonora; Ortenzi, Angela; Colantoni, Alfredo; Sica, Giuseppe; Sileri, Pierpaolo; Rosado, M. Manuela; Carsetti, Rita; Macdonald, Thomas T.; Pallone, Francesco; Monteleone, Giovanni.

In: Journal of Immunology, Vol. 192, No. 12, 15.06.2014, p. 6083-6091.

Research output: Contribution to journalArticle

Cupi, ML, Sarra, M, Marafini, I, Monteleone, I, Franzè, E, Ortenzi, A, Colantoni, A, Sica, G, Sileri, P, Rosado, MM, Carsetti, R, Macdonald, TT, Pallone, F & Monteleone, G 2014, 'Plasma cells in the mucosa of patients with inflammatory bowel disease produce granzyme B and possess cytotoxic activities', Journal of Immunology, vol. 192, no. 12, pp. 6083-6091. https://doi.org/10.4049/jimmunol.1302238
Cupi, Maria Laura ; Sarra, Massimiliano ; Marafini, Irene ; Monteleone, Ivan ; Franzè, Eleonora ; Ortenzi, Angela ; Colantoni, Alfredo ; Sica, Giuseppe ; Sileri, Pierpaolo ; Rosado, M. Manuela ; Carsetti, Rita ; Macdonald, Thomas T. ; Pallone, Francesco ; Monteleone, Giovanni. / Plasma cells in the mucosa of patients with inflammatory bowel disease produce granzyme B and possess cytotoxic activities. In: Journal of Immunology. 2014 ; Vol. 192, No. 12. pp. 6083-6091.
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