Accepted Manuscript Nod-like receptor pyrin-containing protein 6 (NLRP6) is upregulated in ileal Crohn’s disease and differentially expressed in goblet cells Nicole Ranson, Mark Veldhuis, Brent Mitchell, Scott Fanning, Anthony L. Cook, Dale Kunde, Rajaraman Eri
PII: DOI: Reference:
S2352-345X(18)30052-3 10.1016/j.jcmgh.2018.03.001 JCMGH 345
To appear in: Cellular and Molecular Gastroenterology and Hepatology Accepted Date: 5 March 2018 Please cite this article as: Ranson N, Veldhuis M, Mitchell B, Fanning S, Cook AL, Kunde D, Eri R, Nodlike receptor pyrin-containing protein 6 (NLRP6) is upregulated in ileal Crohn’s disease and differentially expressed in goblet cells, Cellular and Molecular Gastroenterology and Hepatology (2018), doi: 10.1016/ j.jcmgh.2018.03.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Nod-like receptor pyrin-containing protein 6 (NLRP6) is upregulated in ileal Crohn’s disease and differentially expressed in goblet cells
Ileal Crohn’s disease
ACCEPTED MANUSCRIPT
Research Letter: Nod-like receptor pyrin-containing protein 6 (NLRP6) is upregulated in ileal Crohn’s disease and differentially expressed in goblet cells 1
2,3
2,3
2,3
4
1
Nicole Ranson , Mark Veldhuis , Brent Mitchell , Scott Fanning , Anthony L. Cook , Dale Kunde 1
RI PT
and Rajaraman Eri
_________________________________________________________________________________ School of Health Sciences, University of Tasmania, Launceston, Tasmania, 7250, Australia
2
Launceston General Hospital, Launceston, Tasmania, 7250, Australia
3
St Vincent’s Hospital, Calvary Health Care, Launceston, Tasmania, 7250, Australia
M AN U
4
SC
1
Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania,
Hobart, Tasmania, 7000, Australia
_________________________________________________________________________________
TE D
Correspondence: Dr Rajaraman Eri, DVM, PhD, School of Health Sciences, University of Tasmania, Locked Bag 1322, Launceston, 7250, Tasmania, Australia. Email:
[email protected] Telephone: +61 363245467, Fax: +61 36243995
EP
Author Contributions: Nicole Ranson, Anthony Cook and Rajaraman Eri conceived and designed the experiments. Nicole Ranson performed laboratory analyses, and wrote the manuscript. Brent
AC C
Mitchell, Scott Fanning and Mark Veldhuis collected biopsy samples. Dale Kunde analysed RNA sequencing data. All authors critically reviewed the manuscript before submission. Conflicts of interest: The authors disclose no conflicts of interest. Funding Support: Funding for this project was obtained from the Clifford Craig Medical Research Trust, PO Box 1963, Launceston, Tasmania, 7250, Australia. An Australian Government Research Training Program Scholarship provided student support. Provenance and peer review: Not commissioned; internally peer reviewed.
1
ACCEPTED MANUSCRIPT A contributing factor in the development of ulcerative colitis (UC) and Crohn’s disease (CD) is aberrant signalling of the innate immune complex known as the inflammasome. The inflammasome regulates the production of IL-1β and drives downstream inflammatory pathways. In this study of human tissue (Ethics approval No: H11930), we provide evidence for the disease specific upregulation of NLRP6 transcript and protein in ileal CD and describe an NLRP6 expressing goblet
RI PT
cell (GC) located predominantly in the upper portion of the intestinal crypt. Patient demographic details are provided in Supplementary Table 1.
Using paired quiescent and active biopsies from UC and CD patients we found that the expression of
SC
NLRP6 increased with disease activity. In ileal CD we report a 131-fold (p
