Lack of the purinergic receptor P2X(7) results in resistance to contact hypersensitivity.
Sensitization to contact allergens requires activation of the innate immune system by endogenous danger signals. However, the mechanisms through which contact allergens activate innate signaling pathways are incompletely understood. In this study, we demonstrate that mice lacking the adenosine triphosphate (ATP) receptor P2X(7) are resistant to contact hypersensitivity (CHS). P2X(7)-deficient dendritic cells fail to induce sensitization to contact allergens and do not release IL-1β in response to lipopolysaccharide (LPS) and ATP. These defects are restored by pretreatment with LPS and alum in an NLRP3- and ASC-dependent manner. Whereas pretreatment of wild-type mice with P2X(7) antagonists, the ATP-degrading enzyme apyrase or IL-1 receptor antagonist, prevents CHS, IL-1β injection restores CHS in P2X(7)-deficient mice. Thus, P2X(7) is a crucial receptor for extracellular ATP released in skin in response to contact allergens. The lack of P2X(7) triggering prevents IL-1β release, which is an essential step in the sensitization process. Interference with P2X(7) signaling may be a promising strategy for the prevention of allergic contact dermatitis.
Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, D-79104 Freiburg, Germany.
Felix C
FC
Weber
Philipp R
PR
Esser
Tobias
T
Müller
Jayanthi
J
Ganesan
Patrizia
P
Pellegatti
Markus M
MM
Simon
Robert
R
Zeiser
Marco
M
Idzko
Thilo
T
Jakob
Stefan F
SF
Martin
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D003877:Dermatitis, Contact / Q000209:etiology / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D058486:Receptors, Purinergic P2X7 / Q000172:deficiency / Q000502:physiology*; D014302:Trinitrobenzenesulfonic Acid
D000534:Alum Compounds; D053583:Interleukin-1beta; D058486:Receptors, Purinergic P2X7; C041524:aluminum sulfate; D000255:Adenosine Triphosphate; D014302:Trinitrobenzenesulfonic Acid