Efficient dendritic cell priming of T lymphocytes depends on the extracellular matrix protein mindin.
Rho guanosine triphosphatases (GTPases) regulate multiple aspects of dendritic cell (DC) function, but what regulates the expression of Rho GTPases in DCs is unknown. Here, we show that the extracellular matrix protein mindin regulates the expression of Rho GTPases in DCs. Mindin(-/-) mice displayed defective CD4+ T-cell priming and impaired humoral immune responses to T-dependent antigens. Mindin(-/-) DCs had reduced expression of Rac1/2 and impaired priming capacity owing to inefficient engagement with T lymphocytes. Ectopic Rac1 expression restored the priming capability of Mindin(-/-) DCs. Furthermore, we show that DC adhesion to mindin matrix was blocked by antibodies to alpha4, alpha5 and beta1 integrins. DCs lacking beta1 integrin had reduced adhesion to mindin matrix, decreased expression of Rac1/2 and impaired priming capacity. These results suggest that mindin-integrin interactions play a key role in regulating Rho GTPase expression in DCs and DC priming of T lymphocytes.
Li
Hong
H
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Oliver
Tim
T
Jia
Wei
W
He
You-Wen
YW
D000818:Animals; D000917:Antibody Formation; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002448:Cell Adhesion; D003713:Dendritic Cells / Q000276:immunology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D016023:Integrins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000097766:RAC2 GTP-Binding Protein
D016326:Extracellular Matrix Proteins; D016023:Integrins; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein; C121491:mindin