CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells

Abstract

Recent studies have challenged the view that Langerhans cells (LCs) constitute the exclusive antigen-presenting cells of the skin and suggest that the dermal dendritic cell (DDC) network is exceedingly complex. Using knockin mice to track and ablate DCs expressing langerin (CD207), we discovered that the dermis contains five distinct DC subsets and identified their migratory counterparts in draining lymph nodes. Based on this refined classification, we demonstrated that the quantitatively minor CD207+ CD103+ DDC subset is endowed with the unique capability of cross-presenting antigens expressed by keratinocytes irrespective of the presence of LCs. We further showed that Y-Ae, an antibody that is widely used to monitor the formation of complexes involving I-Ab molecules and a peptide derived from the I-E α chain, recognizes mature skin DCs that express I-Ab molecules in the absence of I-E α. Knowledge of this extra reactivity is important because it could be, and already has been, mistakenly interpreted to support the view that antigen transfer can occur between LCs and DDCs. Collectively, these data revisit the transfer of antigen that occurs between keratinocytes and the five distinguishable skin DC subsets and stress the high degree of functional specialization that exists among them.

Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4+ T cells but are incapable of cross‐presentation

“…Murine LCs were reported to cross-present antigens [14] although a role for Langerin 1 dermal DCs was not excluded. More recently, in vivo studies indicate that murine Langerin 1 dermal DCs, but not LCs, are responsible for the induction of CD8 1 T-cell responses [38,39]. Our data show that human primary LCs cannot cross-present UV-inactivated MV and MV-infected apoptotic cells in vitro.…”

Existence of CD8α-Like Dendritic Cells with a Conserved Functional Specialization and a Common Molecular Signature in Distant Mammalian Species

“…Finally, they have the ability to export engulfed materials to the cytosol (13). Recently, a similar functional specialization for CD8 + T cell activation has been ascribed to non-LT migratory CD103 + DCs in the lung (14), intestine (15), and skin (16)(17)(18). Interestingly, most of the non-LT CD103 + DCs, except gut CD11b + CD103 + DCs, were found to be related to the LT CD8a + DCs in that they derive from the same precursor in a pathway depending on FLT3 ligand, inhibitor of DNA protein 2 (ID2), and IFN regulatory protein 8 (IRF8) (19,20).…”

Novel insights into the role of immune cells in skin and inducible skin-associated lymphoid tissue (iSALT)

“…From the recent literatures [46,47,48], besides pDCs that are absent from the skin in the steady state, at least ve DC populations are identi ed in the murine dermis: LCs in transit, monocyte-derived DCs that originate from Ly6C + blood monocytes, and dermal conventional DCs (cDCs) that originate from blood-borne precursors. cDCs consist of XC-chemokine receptor 1 (XCR1) + cDCs, CD11b + cDCs, and XCR1 -CD11b -double negative (DN) cDCs [49,50,51].…”