PT  - JOURNAL ARTICLE
AU  - Marta E Polak
AU  - Sofia Sirvent
AU  - Kalum Clayton
AU  - James Davies
AU  - Andres F. Vallejo
AU  - Zhiguo Wu
AU  - Jeongmin Woo
AU  - Jeremy Riddell
AU  - Patrick Stumpf
AU  - Matthew Rose-Zerilli
AU  - Jonathan West
AU  - Mario Pujato
AU  - Xiaoting Chen
AU  - Christopher H. Woelk
AU  - Ben MacArthur
AU  - Michael Ardern-Jones
AU  - Peter S Friedmann
AU  - Matthew T. Weirauch
AU  - Harinder Singh
TI  - Genomic programming of antigen cross-presentation in IRF4-expressing human Langerhans cells
AID  - 10.1101/541383
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 541383
4099  - http://biorxiv.org/content/early/2019/02/05/541383.short
4100  - http://biorxiv.org/content/early/2019/02/05/541383.full
AB  - 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.