TITLE

Small Intestine Inflammation in Roquin-Mutant and Roquin-Deficient Mice

AUTHOR(S)
Schaefer, Jeremy S.; Montufar-Solis, Dina; Nakra, Niyati; Vigneswaran, Nadarajah; Klein, John R.
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Roquin, an E3 ubiquitin ligase that localizes to cytosolic RNA granules, is involved in regulating mRNA stability and translation. Mice that have a M199R mutation in the Roquin protein (referred to as sanroque or Roquinsan/san mice) develop autoimmune pathologies, although the extent to which these occur in the intestinal mucosa has not been determined. Here, we demonstrate that Roquinsan/san mice reproducibly develop intestinal inflammation in the small intestine but not the colon. Similarly, mice generated in our laboratory in which the Roquin gene was disrupted by insertion of a gene trap cassette (Roquingt/gt mice) had small intestinal inflammation that mimicked that of Roquinsan/san mice. MLN cells in Roquinsan/san mice consisted of activated proliferating T cells, and had increased numbers of CD44hi CD62Llo KLRG1+ short-lived effector cells. Proportionally more small intestinal intraepithelial lymphocytes in Roquinsan/san mice expressed the ICOS T cell activation marker. Of particular interest, small intestinal lamina propria lymphocytes in Roquinsan/san mice consisted of a high proportion of Gr-1+ T cells that included IL-17A+ cells and CD8+ IFN-γ+ cells. Extensive cytokine dysregulation resulting in both over-expression and under-expression of chemotactic cytokines occurred in the ileum of Roquinsan/san mice, the region most prone to the development of inflammation. These findings demonstrate that chronic inflammation ensues in the intestine following Roquin alteration either as a consequence of protein mutation or gene disruption, and they have implications for understanding how small intestinal inflammation is perpetuated in Crohn's disease (CD). Due to the paucity of animal models of CD-like pathophysiology in the small intestine, and because the primary gene/protein defects of the Roquin animal systems used here are well-defined, it will be possible to further elucidate the underlying genetic and molecular mechanisms that drive the disease process.
ACCESSION #
87624606

 

Related Articles

  • Autoimmunity: The worm returns. Weinstock, Joel V. // Nature;11/8/2012, Vol. 491 Issue 7423, p183 

    The author discusses several parasitic worms such as roundworms and helminths. He mentions the relative increase in new diseases caused by the parasitic worms such as inflammatory bowel disease. He cites his research which looks on whether getting rid of parasitic worms and beneficial bacteria...

  • Peli1 sets the CNS on fire. Song, Xinyang; Qian, Youcun // Nature Medicine;May2013, Vol. 19 Issue 5, p536 

    The article offers information on the E3 ubiquitin ligase Peli1 which was identified as an important regulator of microglia activation during the pathogenesis of experimental autoimmune encephalomyelitis (EAE). It says that the essential role of Peli1 was recognized by using mouse model of human...

  • Cancer: IL-22: linking inflammation and cancer. Harrison, Charlotte // Nature Reviews Drug Discovery;Jul2013, Vol. 12 Issue 7, p504 

    The article discusses research being done on the role of interleukin-22 (IL-22) in the transition from intestinal inflammation to cancer. It references a study by S. Kirchberger et al published in a 2013 issue of the "Journal of Experimental Medicine." Mice served as subjects in this study....

  • Suppressor of cytokine signalling 1 in lymphocytes regulates the development of intestinal inflammation in mice. K. Inagaki-Ohara; A. Sasaki; G. Matsuzaki; I. Ikeda; M. Hotokezaka; K. Chijiiwa; M. Kubo; H. Yoshida; Y. Nawa; A. Yoshimura // Gut;Feb2006, Vol. 55 Issue 2, p212 

    Background and aims: Imbalance between pro- and anti-inflammatory cytokines produced by intestinal T cells induces inflammatory bowel diseases (IBD). However, the importance of regulation of cytokine signalling in IBD has not been fully clarified. We have demonstrated that suppressor of cytokine...

  • Vitamin D Deficiency Is Associated with Ulcerative Colitis Disease Activity. Blanck, Stacey; Aberra, Faten // Digestive Diseases & Sciences;Jun2013, Vol. 58 Issue 6, p1698 

    Purpose: Previous studies on experimental mouse models have suggested a role of vitamin D in immune system regulation and IBD disease severity. In this study, we examine the relationship between vitamin D levels and clinical disease activity in human subjects with ulcerative colitis (UC). We...

  • The Novel Ubiquitin Ligase Complex, SCFFbxw4, Interacts with the COP9 Signalosome in an F-Box Dependent Manner, Is Mutated, Lost and Under-Expressed in Human Cancers Lockwood, William W.; Chandel, Sahiba K.; Stewart, Greg L.; Erdjument-Bromage, Hediye; Beverly, Levi J. // PLoS ONE;May2013, Vol. 8 Issue 5, p1 

    Identification of novel proteins that can potentially contribute to carcinogenesis is a requisite venture. Herein, we report the first biochemical characterization of the novel F-box and WD40 containing protein, FBXW4. We have identified interacting protein partners and demonstrated that FBXW4...

  • IL-19 as a Potential Therapeutic in Autoimmune and Inflammatory Diseases. Azuma, Yasu-Taka; Nakajima, Hidemitsu; Takeuchi, Tadayoshi // Current Pharmaceutical Design;11/21/2011, Vol. 17 Issue 34, p3776 

    Interleukin-19 (IL-19) is a member of the IL-10 family of cytokines. The last ten years from the finding of IL-19, investigations underline the role of IL-19 in the immunological diseases. It is known that expression of IL-19 is increased in the epidermis of patients with psoriasis, which is a...

  • Therapeutic Effects of Novel Sphingosine-1-Phosphate Receptor Agonist W-061 in Murine DSS Colitis. Sanada, Yasuaki; Mizushima, Tsunekazu; Kai, Yasuyuki; Nishimura, Junichi; Hagiya, Hiroshi; Kurata, Haruto; Mizuno, Hirotaka; Uejima, Etsuko; Ito, Toshinori // PLoS ONE;2011, Vol. 6 Issue 9, p1 

    Although IL-17 is a pro-inflammatory cytokine reportedly involved in various autoimmune inflammatory disorders, its role remains unclear in murine models of colitis. Acute colitis was induced by 2.5% dextran sodium sulfate (DSS) treatment for 5 days. A novel sphingosine-1-phosphate receptor...

  • Amelioration of Dextran Sodium Sulfate-Induced Colitis in Mice by Rhodobacter sphaeroides Extract. Wen-Sheng Liu; Man-Chin Chen; Kuo-Hsun Chiu; Zhi-Hong Wen; Che-Hsin Lee // Molecules;Nov2012, Vol. 17 Issue 11, p13622 

    Bacteria can produce some compounds in response to their environment. These compounds are widely used in cosmetic and pharmaceutical applications. Some probiotics have immunomodulatory activities and modulate the symptoms of several diseases. Autoimmune diseases represent a complex group of...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics