Accumulation of HLA-DR4 in Colonic Epithelial Cells Causes Severe Colitis in Homozygous HLA-DR4 Transgenic Mice

Inflammatory Bowel Diseases
Atsushi IrieYasuharu Nishimura

Abstract

Homozygous HLA-DR4/I-E transgenic mice (tgm) spontaneously developed colitis similar to human ulcerative colitis. We explored whether endoplasmic reticulum stress in colonic epithelial cells due to overexpression of HLA-DR4/I-E was involved in the pathogenesis of colitis. Major histocompatibility complex class II transactivator-knockout (CIITAKO) background tgm were established to test the involvement of HLA-DR4/I-E expression in the pathogenesis of colitis. Histological and cellular analyses were performed and the effect of oral administration of the molecular chaperone tauroursodeoxycholic acid (TUDCA) and antibiotics were investigated. IgA content of feces and serum and presence of IgA-coated fecal bacteria were also investigated. Aberrantly accumulated HLA-DR4/I-E molecules in colonic epithelial cells were observed only in the colitic homozygous tgm, which was accompanied by upregulation of the endoplasmic reticulum stress marker Binding immunoglobulin protein (BiP) and reduced mucus. Homozygous tgm with CIITAKO, and thus absent of HLA-DR4/I-E expression, did not develop colitis. Oral administration of TUDCA to homozygotes reduced HLA-DR4/I-E and BiP expression in colonic epithelial cells and restored the barrier function o...Continue Reading

References

Nov 1, 1995·The Journal of Experimental Medicine·M F NeurathW Strober
Mar 25, 1995·Nucleic Acids Research·P D SiebertS A Lukyanov
Jul 1, 1994·The Journal of Experimental Medicine·A WoodsD M Zaller
Aug 18, 1999·Immunological Reviews·J D TaurogR E Hammer
Mar 10, 2001·The Journal of Clinical Investigation·A BertolottiD Ron
Nov 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·M A FarmerE H Leiter
Jun 18, 2004·European Journal of Gastroenterology & Hepatology·Laurens A van der WaaijJohn O Hunter
Oct 4, 2005·Nature Reviews. Immunology·Walter ReithJean-Marc Waldburger
Mar 3, 2007·The Journal of Clinical Investigation·Warren StroberPeter Mannon
Jul 27, 2007·Nature·R J Xavier, D K Podolsky
Feb 25, 2009·Seminars in Immunology·Arthur Kaser, Richard S Blumberg
Oct 27, 2009·Inflammatory Bowel Diseases·Andre BleichEdward H Leiter
Mar 3, 2010·Annual Review of Immunology·Arthur KaserRichard S Blumberg
Jul 14, 2010·Nature Reviews. Microbiology·Sandra NellChristine Josenhans
Sep 10, 2011·Antioxidants & Redox Signaling·Izabela LenartAntony N Antoniou
May 30, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yusuke TomitaYasuharu Nishimura
Oct 4, 2013·Nature·Timon E AdolphRichard S Blumberg
Oct 10, 2013·Gut·Joana TorresJean-Frédéric Colombel
Feb 26, 2014·Nature Reviews. Immunology·Lance W Peterson, David Artis

❮ Previous
Next ❯

Citations

Sep 14, 2019·Alimentary Pharmacology & Therapeutics·James J AshtonSarah Ennis
Aug 28, 2020·Drug Metabolism Reviews·Takeshi SusukidaKousei Ito
Aug 2, 2019·World Journal of Gastroenterology : WJG·Alexandre Loktionov

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.