Back to Search
Start Over
Guanine nucleotide-binding proteins of the G12 family shape immune functions by controlling CD4+ T cell adhesiveness and motility.
- Source :
-
Immunity [Immunity] 2009 May; Vol. 30 (5), pp. 708-20. Date of Electronic Publication: 2009 Apr 30. - Publication Year :
- 2009
-
Abstract
- Integrin-mediated adhesion plays a central role in T cell trafficking and activation. Genetic inactivation of the guanine nucleotide-binding (G) protein alpha-subunits Galpha(12) and Galpha(13) resulted in an increased activity of integrin leukocyte-function-antigen-1 in murine CD4(+) T cells. The interaction with allogeneic dendritic cells was enhanced, leading to an abnormal proliferative response in vitro. In vivo, T cell-specific inactivation of Galpha(12) and Galpha(13) caused lymphadenopathy due to increased lymph node entry and enhanced T cell proliferation, and the susceptibility toward T cell-mediated diseases was enhanced. Mechanistically, we show that in the absence of Galpha(12) and Galpha(13) the activity of the small GTPases Rac1 and Rap1 was increased, whereas signaling of the small GTPase RhoA was strongly reduced. Our data indicate that locally produced mediators signal through Galpha(12)- and Galpha(13)-coupled receptors to negatively regulate cell polarization and adhesiveness, thereby fine-tuning T cell trafficking, proliferation, and susceptibility toward T cell-mediated diseases.
- Subjects :
- Animals
CD4-Positive T-Lymphocytes cytology
CD4-Positive T-Lymphocytes enzymology
Cell Adhesion immunology
Cell Movement immunology
Cell Proliferation
Dendritic Cells cytology
Dendritic Cells metabolism
GTP-Binding Protein alpha Subunits, G12-G13 genetics
GTP-Binding Protein alpha Subunits, G12-G13 immunology
Intercellular Adhesion Molecule-1 immunology
Intercellular Adhesion Molecule-1 metabolism
Lymphocyte Function-Associated Antigen-1 immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Neuropeptides immunology
Neuropeptides metabolism
Signal Transduction immunology
Telomere-Binding Proteins immunology
Telomere-Binding Proteins metabolism
Vascular Cell Adhesion Molecule-1 immunology
Vascular Cell Adhesion Molecule-1 metabolism
rac GTP-Binding Proteins immunology
rac GTP-Binding Proteins metabolism
rac1 GTP-Binding Protein
rhoA GTP-Binding Protein immunology
rhoA GTP-Binding Protein metabolism
CD4-Positive T-Lymphocytes immunology
Dendritic Cells immunology
GTP-Binding Protein alpha Subunits, G12-G13 metabolism
Lymphocyte Function-Associated Antigen-1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4180
- Volume :
- 30
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 19409815
- Full Text :
- https://doi.org/10.1016/j.immuni.2009.02.010