CD39 is the dominant Langerhans cell-associated ecto-NTPDase: modulatory roles in inflammation and immune responsiveness.
CD39, the endothelial ecto-nucleoside triphosphate diphosphohydrolase (NTPDase), regulates vascular inflammation and thrombosis by hydrolyzing ATP and ADP. Although ecto-NTPDase activities have been used as a marker of epidermal dendritic cells (DCs) known as Langerhans cells, the identity and function of these activities remain unknown. Here we report that Langerhans cells in CD39-/- mice express no detectable ecto-NTPDase activity. Irritant chemicals triggered rapid ATP and ADP release from keratinocytes and caused exacerbated skin inflammation in CD39-/- mice. Paradoxically, T cell-mediated allergic contact hypersensitivity was severely attenuated in CD39-/- mice. As to mechanisms, T cells increased pericellular ATP concentrations upon activation, and CD39-/- DCs showed ATP unresponsiveness (secondary to P2-receptor desensitization) and impaired antigen-presenting capacity. Our results show opposing outcomes of CD39 deficiency in irritant versus allergic contact dermatitis, reflecting its diverse roles in regulating extracellular nucleotide-mediated signaling in inflammatory responses to environmental insults and DC-T cell communication in antigen presentation.
Mizumoto
Norikatsu
N
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Kumamoto
Tadashi
T
Robson
Simon C
SC
Sévigny
Jean
J
Matsue
Hiroyuki
H
Enjyoji
Keiichi
K
Takashima
Akira
A
D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D001081:Apyrase; D005260:Female; D007109:Immunity; D007249:Inflammation / Q000201:enzymology* / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D007509:Irritants / Q000633:toxicity; D007801:Langerhans Cells / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018048:Receptors, Purinergic P2 / Q000502:physiology; D015398:Signal Transduction
D015703:Antigens, CD; D007509:Irritants; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D001081:Apyrase; C067869:CD39 antigen