Differential regulation of Th2 and Th1 lung inflammatory responses by protein kinase C theta.
In vitro and recent in vivo studies have identified protein kinase Ctheta (PKCtheta) as an important intermediate in signaling pathways leading to T cell activation, proliferation, and cytokine production. However, the importance of PKCtheta to many T cell-driven inflammatory responses has not been demonstrated. In this study we show that although PKCtheta is required for the development of a robust lung inflammatory response controlled by Th2 cells, it plays a lesser role in the development of a similar lung inflammatory response controlled by Th1 cells. PKCtheta-deficient mice were strongly compromised in generating Th2 cells and exhibited reduced airway eosinophilia and Th2 cytokine production in lungs. PKCtheta was required for the initial development of Th1 cells, with these cells exhibiting delayed kinetics of differentiation and accumulation. However, with recall Ag challenge via the airways, this defect was overcome, and lung infiltration and Th1 cytokine production were largely unimpaired in PKCtheta-deficient animals. These data suggest that PKCtheta can play roles in aspects of both Th2 and Th1 responses, but lung inflammation induced by Th2 cells is more dependent on this protein kinase than lung inflammation induced by Th1 cells.
Salek-Ardakani
Shahram
S
Division Molecular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, La Jolla, CA 92121, USA.
So
Takanori
T
Halteman
Beth S
BS
Altman
Amnon
A
Croft
Michael
M
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018106:CD28 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002449:Cell Aggregation / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D018960:Hyaluronan Receptors / Q000502:physiology; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000074121:Protein Kinase C-theta; D018417:Th1 Cells / Q000201:enzymology* / Q000276:immunology / Q000473:pathology*; D018418:Th2 Cells / Q000201:enzymology* / Q000276:immunology / Q000473:pathology*
D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D018960:Hyaluronan Receptors; D007527:Isoenzymes; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta