McNamee, Eóin N. and Masterson, Joanne C. and Jedlicka, Paul and McManus, Martine and Grenz, Almut and Collins, Colm B. and Nold, Marcel F. and Nold-Petry, Claudia and Bufler, Philip and Dinarello, Charles A. and Rivera-Nieves, Jesus
(2011)
Interleukin 37 expression protects mice from colitis.
Proceedings of the National Academy of Sciences of the United States of America, 108 (40).
pp. 16711-16716.
ISSN 0027-8424
Abstract
IL-37, a newly described member of the IL-1 family, functions as
a fundamental inhibitor of innate inflammation and immunity. In
the present study, we examined a role for IL-37 during experimental colitis. A transgenic mouse strain was generated to express
human IL-37 (hIL-37tg), and these mice were subjected to dextran
sulfate sodium (DSS)-induced colitis. Despite the presence of
a CMV promoter to drive expression of IL-37, mRNA transcripts
were not present in colons at the resting state. Expression was
observed only upon disruption of the epithelial barrier, with
a six- to sevenfold increase (P = 0.02) on days 3 and 5 after continuous exposure to DSS. During the development of colitis, clinical disease scores were reduced by 50% (P < 0.001), and
histological indices of colitis were one-third less in hIL-37tg mice
compared with WT counterparts (P < 0.001). Reduced inflammation was associated with decreased leukocyte recruitment into the
colonic lamina propria. In addition, release of IL-1β and TNFα from
ex vivo colonic explant tissue was decreased 5- and 13-fold, respectively, compared with WT (P £ 0.005), whereas IL-10 was increased sixfold (P < 0.001). However, IL-10 was not required for
the anti-inflammatory effects of IL-37 because IL-10-receptor antibody blockade did not reverse IL-37-mediated protection. Mechanistically, IL-37 originating from hematopoietic cells was sufficient
to exert anti-inflammatory effects because WT mice reconstituted
with hIL-37tg bone marrow were protected from colitis. Thus, IL-37
emerges as key modulator of intestinal inflammation.
| Item Type: |
Article
|
| Keywords: |
Interleukin 37 expression; protects mice; colitis; cytokine; intestine; inflammatory bowel disease; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
12499 |
| Identification Number: |
https://doi.org/10.1073/pnas.1111982108 |
| Depositing User: |
Joanne Masterson
|
| Date Deposited: |
27 Feb 2020 16:39 |
| Journal or Publication Title: |
Proceedings of the National Academy of Sciences of the United States of America |
| Publisher: |
National Academy of Sciences |
| Refereed: |
Yes |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
Repository Staff Only(login required)
 |
Item control page |
Downloads per month over past year
Origin of downloads
Altmetric
Altmetric