Calcitonin gene-related peptide decreases expression of HLA-DR and CD86 by human dendritic cells and dampens dendritic cell-driven T cell-proliferative responses via the type I calcitonin gene-related peptide receptor.
These studies were performed to establish whether functional receptors for calcitonin gene-related peptide (CGRP) are present on human dendritic cells (DCs) and to investigate potential immunomodulatory effects of CGRP on DCs other than Langerhans cells. Reverse transcriptase-PCR revealed expression of mRNA for a type 1 CGRP receptor by mature and immature blood-derived DCs. Sequence analysis confirmed the identity of the type 1 CGRP receptor (CGRP-R1). Addition of CGRP (10-7 M) to mature and immature DCs resulted in mobilization of intracellular calcium. Treatment of immature DCs with CGRP (10-7 M), before and after maturation in monocyte-conditioned medium, resulted in decreased cell surface expression of HLA-DR MHC class II and the costimulatory molecule, CD86. Treatment of immature DCs with CGRP (10-7 M) also resulted in decreased expression of CD86, but expression of HLA-DR was unchanged. When CGRP-treated mature DCs were used to stimulate allogeneic T cells, proliferative responses were dampened (approximately 50%), especially at low DC:T cell ratios (1:360). This effect was not observed with CGRP-treated, immature DCs. In contrast, CGRP-treated mature or immature DCs were no less efficient than untreated DCs in driving syngeneic T cell-proliferative responses to staphylococcal enterotoxin B. We conclude that mature and immature DCs express type 1 CGRP receptors and that signaling through these receptors may dampen mature DC-driven T cell proliferation most likely via down-regulation of CD86 and HLA-DR.
Carucci
J A
JA
Laboratories of Cellular Physiology Rockefeller University, New York, NY 10021, USA.
Ignatius
R
R
Wei
Y
Y
Cypess
A M
AM
Schaer
D A
DA
Pope
M
M
Steinman
R M
RM
Mojsov
S
S
D015703:Antigens, CD / Q000096:biosynthesis* / Q000494:pharmacology; D051940:B7-2 Antigen; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004768:Enterotoxins / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000502:physiology*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D004768:Enterotoxins; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D007519:Isoantigens; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018015:Receptors, Calcitonin Gene-Related Peptide; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium