Granzyme M has a critical role in providing innate immune protection in ulcerative colitis

Souza-Fonseca-Guimaraes, F., Krasnova, Y., Putoczki, T., Miles, K., MacDonald, K. P., Town, L., Shi, W., Gobe, G. C., McDade, L., Mielke, L. A., Tye, H., Masters, S. L., Belz, G. T., Huntington, N. D., Radford-Smith, G. and Smyth, M. J. (2016) Granzyme M has a critical role in providing innate immune protection in ulcerative colitis. Cell Death and Disease, 7 e2302. doi:10.1038/cddis.2016.215


Author Souza-Fonseca-Guimaraes, F.
Krasnova, Y.
Putoczki, T.
Miles, K.
MacDonald, K. P.
Town, L.
Shi, W.
Gobe, G. C.
McDade, L.
Mielke, L. A.
Tye, H.
Masters, S. L.
Belz, G. T.
Huntington, N. D.
Radford-Smith, G.
Smyth, M. J.
Title Granzyme M has a critical role in providing innate immune protection in ulcerative colitis
Journal name Cell Death and Disease   Check publisher's open access policy
ISSN 2041-4889
Publication date 2016-07-01
Sub-type Article (original research)
DOI 10.1038/cddis.2016.215
Open Access Status DOI
Volume 7
Start page e2302
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 2403 Immunology
2804 Cellular and Molecular Neuroscience
1307 Cell Biology
1306 Cancer Research
Abstract Inflammatory bowel disease (IBD) is an immunoregulatory disorder, associated with a chronic and inappropriate mucosal immune response to commensal bacteria, underlying disease states such as ulcerative colitis (UC) and Crohn’s disease (CD) in humans. Granzyme M (GrzM) is a serine protease expressed by cytotoxic lymphocytes, in particular natural killer (NK) cells. Granzymes are thought to be involved in triggering cell death in eukaryotic target cells; however, some evidence supports their role in inflammation. The role of GrzM in the innate immune response to mucosal inflammation has never been examined. Here, we discover that patients with UC, unlike patients with CD, display high levels of GrzM mRNA expression in the inflamed colon. By taking advantage of well-established models of experimental UC, we revealed that GrzM-deficient mice have greater levels of inflammatory indicators during dextran sulfate sodium (DSS)-induced IBD, including increased weight loss, greater colon length reduction and more severe intestinal histopathology. The absence of GrzM expression also had effects on gut permeability, tissue cytokine/chemokine dynamics, and neutrophil infiltration during disease. These findings demonstrate, for the first time, that GrzM has a critical role during early stages of inflammation in UC, and that in its absence colonic inflammation is enhanced.
Keyword Inflammatory bowel disease
Natural killer cells
NK-cell
Serine-protease
In-vivo
T-cell
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Article number e2302

Document type: Journal Article
Sub-type: Article (original research)
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