Pituitary adenylate cyclase-activating polypeptide inhibits cutaneous immune function.
Epidermal nerves are closely associated with Langerhans cells (LC) and may be able to release factors, such as calcitonin gene-related peptide and epinephrine, that affect LC function. LC and the LC-like cell line XS106 express mRNA for the pituitary adenylate cyclase-activating polypeptide (PACAP) receptors VPAC1 and VPAC2. We examined whether PACAP regulates cutaneous immunity. Intradermal administration of PACAP prior to application of a contact sensitizer at the injected site inhibited the induction of contact hypersensitivity. Pretreatment of murine epidermal cells enriched for LC content (approximately 12% LC) with PACAP inhibited their ability to elicit delayed-type hypersensitivity in previously immunized mice. In vitro, PACAP suppressed the ability of both murine epidermal cells and highly purified LC (approximately 95%) to present antigen to a T cell clone and hybridoma. Furthermore, in LC and the XS106 cell line, PACAP inhibited the LPS/GM-CSF-induced stimulation of IL-1beta secretion and augmented IL-10 production. PACAP also down-regulated CD86 expression in LPS/GM-CSF-stimulated XS106 cells. The immunosuppressive effects of PACAP may be due to modulation of cytokine production and CD86 expression.
Kodali
Sreedevi
S
Department of Dermatology, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY 10021, USA.
Friedman
Ilyse
I
Ding
Wanhong
W
Seiffert
Kristina
K
Wagner
John A
JA
Granstein
Richard D
RD
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D051940:B7-2 Antigen; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism; D006825:Hybridomas / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009479:Neuropeptides / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
C495402:Adcyap1 protein, mouse; D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016753:Interleukin-10