Back to Search
Start Over
CD98hc regulates the development of experimental colitis by controlling effector and regulatory CD4(+) T cells.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2014 Feb 21; Vol. 444 (4), pp. 628-33. Date of Electronic Publication: 2014 Jan 31. - Publication Year :
- 2014
-
Abstract
- CD4(+) T cell activation is controlled by signaling through the T cell receptor in addition to various co-receptors, and is also affected by their interactions with effector and regulatory T cells in the microenvironment. Inflammatory bowel diseases (IBD) are caused by the persistent activation and expansion of auto-aggressive CD4(+) T cells that attack intestinal epithelial cells. However, the molecular basis for the persistent activation of CD4(+) T cells in IBD remains unclear. In this study, we investigated how the CD98 heavy chain (CD98hc, Slc3a2) affected the development of colitis in an experimental animal model. Transferring CD98hc-deficient CD4(+)CD25(-) T cells into Rag2(-/-) mice did not cause colitis accompanied by increasing Foxp3(+) inducible regulatory T cells. By comparison, CD98hc-deficient naturally occurring regulatory T cells (nTregs) had a decreased capability to suppress colitis induced by CD4(+)CD25(-) T cells, although CD98hc-deficient mice did not have a defect in the development of nTregs. Blocking CD98hc with an anti-CD98 blocking antibody prevented the development of colitis. Our results indicate that CD98hc regulates the expansion of autoimmune CD4(+) T cells in addition to controlling nTregs functions, which suggests the CD98hc as an important target molecule for establishing strategies for treating colitis.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Autoimmune Diseases immunology
CD4-Positive T-Lymphocytes metabolism
CD4-Positive T-Lymphocytes pathology
Colitis genetics
Colon immunology
Colon metabolism
DNA-Binding Proteins genetics
Fusion Regulatory Protein 1, Heavy Chain genetics
Gene Deletion
Interleukin-2 Receptor alpha Subunit genetics
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
CD4-Positive T-Lymphocytes immunology
Colitis immunology
Colitis pathology
Colon pathology
Fusion Regulatory Protein 1, Heavy Chain immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 444
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 24491544
- Full Text :
- https://doi.org/10.1016/j.bbrc.2014.01.144