Langerhans cells regulate cutaneous injury by licensing CD8 effector cells recruited to the skin

Clare L. Bennett, Farnaz Fallah-Arani, Thomas Conlan, Celine Trouillet, Hugh Goold, Laurent Chorro, Barry Flutter, Terry K. Means, Frédéric Geissmann, Ronjon Chakraverty

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Langerhans cells (LCs) are a distinct population of dendritic cells that form a contiguous network in the epidermis of the skin. Although LCs possess many of the properties of highly proficient dendritic cells, recent studies have indicated that they are not necessary to initiate cutaneous immunity. In this study, we used a tractable model of cutaneous GVHD, induced by topical application of a Toll-like receptor agonist, to explore the role of LCs in the development of tissue injury. By adapting this model to permit inducible and selective depletion of host LCs, we found that GVHD was significantly reduced when LCs were absent. However, LCs were not required either for CD8 T-cell activation within the draining lymph node or subsequent homing of effector cells to the epidermis. Instead, we found that LCs were necessary for inducing transcription of IFN-γ and other key effector molecules by donor CD8 cells in the epidermis, indicating that they license CD8 cells to induce epithelial injury. These data demonstrate a novel regulatory role for epidermal LCs during the effector phase of an inflammatory immune response in the skin.

Original languageEnglish (US)
Pages (from-to)7063-7069
Number of pages7
JournalBlood
Volume117
Issue number26
DOIs
StatePublished - Jun 30 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Bennett, C. L., Fallah-Arani, F., Conlan, T., Trouillet, C., Goold, H., Chorro, L., Flutter, B., Means, T. K., Geissmann, F., & Chakraverty, R. (2011). Langerhans cells regulate cutaneous injury by licensing CD8 effector cells recruited to the skin. Blood, 117(26), 7063-7069. https://doi.org/10.1182/blood-2011-01-329185