Expression of CD73 slows down migration of skin dendritic cells, affecting the sensitization phase of contact hypersensitivity reactions in mice. Issue 3 (September 2017)

• Record Type: Journal Article
• Authors: Neuberger, A.; Ring, S.; Silva-Vilches, C.; Schrader, J.; Enk, A.; Mahnke, K.
• Is Part Of: Journal of dermatological science. Volume 87:Issue 3(2017:Sep.)
• Page Start: 292
• Page End: 299
• Publication Date: 2017-09
• Subjects: ADO adenosine -- AR ADO receptor -- ATP adenosine triphosphate -- BMDC bone marrow derived DC -- CHS contact hypersensitivity -- DC dendritic cells -- d day -- FCS fetal calf serum -- IFN-γ interferon-γ -- IL interleukin -- LN lymph node -- TNCB 2, 4, 6-trinitrochlorobenzene -- wt wild type; Ectonucleotidases -- Contact hypersensitivity -- Skin dendritic cells; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2017.07.002
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: Skin dendritic cells express CD73. CD73 affects the migration of DC from skin to lymph nodes. Ablation of CD73 results in increased contact hypersensitivity. Abstract: Background: Application of haptens to the skin induces release of immune stimulatory ATP into the extracellular space. This "danger" signal can be converted to immunosuppressive adenosine (ADO) by the action of the ectonucleotidases CD39 and CD73, expressed by skin and immune cells. Thus, the expression and regulation of CD73 by skin derived cells may have crucial influence on the outcome of contact hypersensitivity (CHS) reactions. Objective: To investigate the role of CD73 expression during 2, 4, 6-trinitrochlorobenzene (TNCB) induced CHS reactions. Methods: Wild type (wt) and CD73 deficient mice were subjected to TNCB induced CHS. In the different mouse strains the resulting ear swelling reaction was recorded along with a detailed phenotypic analysis of the skin migrating subsets of dendritic cells (DC). Results: In CD73 deficient animals the motility of DC was higher as compared to wt animals and in particular after sensitization we found increased migration of Langerin + DC from skin to draining lymph nodes (LN). In the TNCB model this led to a stronger sensitization as indicated by increased frequency of interferon-γ producing T cells in the LN and an increased ear thickness after challenge. Conclusion: CD73 derived ADO production slows down migration of Langerin + DC from skin to LN. This may be a crucial mechanism to avoid over boarding immune reactions against haptens.