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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Down-Regulation of CD62L Shedding in T Cells by CD39+ Regulatory T Cells Leads to Defective Sensitization in Contact Hypersensitivity Reactions
Journal of Investigative Dermatology, Volume 137, No. 1, Year 2017
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Description
Injection of regulatory T cells (Tregs) followed by sensitization with 2,4,6-trinitrochlorobenzene induced a transient increase in size and cellularity of skin-draining lymph nodes (LNs) in mice. This led us to hypothesize that Tregs may affect the trafficking of T cells from and to peripheral LNs. Two to three hours after sensitization, we found fewer CD8+ T cells expressing CD62L in LNs compared with untreated controls. Injection of wild-type Tregs prevented this down-regulation of CD62L. In contrast, Tregs devoid of the adenosine triphosphate (ATP)-degrading ecto-enzyme CD39 were unable to do so. As for the mechanism of CD62L regulation, we found that ATP, which is released in skin upon hapten-exposure, is inducing the protease ADAM17 in LN-residing T cells via engagement of P2X7 ATP receptors. ADAM17 cleaves CD62L from the surface of CD8+ T cells, which in turn provide a signal for T cells to leave the LNs. This regulation of CD62L is disturbed by the presence of Tregs, because Tregs remove extracellular ATP from the tissue by activity of CD39 and, therefore, abrogate the shedding of CD62L. Thus, these data indicate that the regulation of ATP turnover by Tregs in skin and LNs is an important modulator for immune responses. © 2016 The Authors
Authors & Co-Authors
Jendrossek, V.
Germany, Duisburg
Universität Duisburg-essen
Robson, Simon Christopher
United States, Boston
Beth Israel Deaconess Medical Center
Steinbrink, Kerstin
Germany, Mainz
Johannes Gutenberg-universität Mainz
Statistics
Citations: 16
Authors: 3
Affiliations: 5
Identifiers
Doi:
10.1016/j.jid.2016.08.023
ISSN:
0022202X