Genomic programming of antigen cross-presentation in IRF4-expressing human Langerhans cells.

Marta E Polak, Sofia Sirvent, Kalum Clayton, James Davies, Andres F. Vallejo, Zhiguo Wu, Jeongmin Woo, Jeremy Riddell, Patrick Stumpf, Matthew RoseZerilli, Jonathan West, Mario Pujato, Xiaoting Chen, Christopher H. Woelk, Ben MacArthur, Michael Ardern-Jones, Peter S Friedmann, Matthew T. Weirauch, Harinder Singh

Feb 21, 2019

Received Date: 5th February 19

Langerhans cells (LCs) in the epidermis present MHC I and MHC II-restricted antigens thereby priming either CD8 or CD4 T cell immune responses. The genomic programs and transcription factors regulating antigen presentation in LCs remain to be elucidated. We show human LCs are highly efficient in MHC I-antigen cross-presentation but lack the transcription factor IRF8 that is critical in dendritic cells. LC migration from the epidermis enhances their ability to cross-present antigens and is accompanied by the induction of the transcription factor IRF4, whose expression is correlated by scRNA-seq with genes involved in ubiquitin-dependent protein degradation. Chromatin profiling reveals enrichment of EICE and AICE composite DNA binding motifs in regulatory regions of antigen-presentation genes, which can be recognized by IRF4 in conjunction with PU.1 or BATF3 expressed in LCs.  Thus, the genomic programming of human LCs including inducible expression of IRF4 with enhanced cross-presentation distinguishes them from conventional dendritic cells.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

Nature Communications

Nature Research, Springer Nature