Ultraviolet irradiation suppresses T cell activation via blocking TCR-mediated ERK and NF-kappa B signaling pathways.
UV irradiation is carcinogenic and immunosuppressive. Previous studies indicate that UV-mediated alteration of APCs and induction of suppressor T cells play a critical role in UV-induced immune suppression. In this study, we show that UV irradiation can directly (independently of APCs and suppressor T cells) inhibit T cell activation by blocking TCR-mediated phosphorylation of ERK and IkappaB via overactivation of the p38 and JNK pathways. These events lead to the down-modulation of c-Jun, c-Fos, Egr-1, and NF-kappaB transcription factors and thereby inhibit production of cytokines, e.g., IL-2, IL-4, IFN-gamma, and TNF-alpha, upon TCR stimulation. We also show that UV irradiation can suppress preactivated T cells, indicating that UV irradiation does not only impair T cell function in response to T cell activation, but can also have systemic effects that influence ongoing immune responses. Thus, our data provide an additional mechanism by which UV irradiation directly suppresses immune responses.
Li-Weber
Min
M
Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany. m.li-weber@dkfz-heidelberg.de
Treiber
Monika K
MK
Giaisi
Marco
M
Palfi
Katalin
K
Stephan
Nadja
N
Parg
Simone
S
Krammer
Peter H
PH
D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004789:Enzyme Activation / Q000528:radiation effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D007165:Immunosuppression Therapy; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000528:radiation effects; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology / Q000528:radiation effects*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology / Q000528:radiation effects; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000528:radiation effects; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000502:physiology / Q000528:radiation effects; D015398:Signal Transduction / Q000276:immunology / Q000528:radiation effects*; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000528:radiation effects
D016207:Cytokines; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D011948:Receptors, Antigen, T-Cell; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases