Defining the landscape of human epidermal mononuclear phagocytes

The stratified squamous epithelium (SSE) forms the epidermis of skin (e.g., trunk skin, foreskin, and labia) and the epithelium of type II mucosal tissues (e.g., vagina, ectocervix, and anal canal). Langerhans cells (LCs) were long thought to be the sole mononuclear phagocyte (MNP) residing in these tissues. However, two decades ago, other MNP populations appearing as dendritic cells (DCs) were reported in inflamed SSE 1 Achachi A. Vocanson M. Bastien P. Péguet-Navarro J. Grande S. Goujon C. Breton L. Castiel-Higounenc I. Nicolas J.F. Gueniche A. UV Radiation Induces the Epidermal Recruitment of Dendritic Cells that Compensate for the Depletion of Langerhans Cells in Human Skin. J. Invest. Dermatol. 2015; 135: 2058-2067https://doi.org/10.1038/jid.2015.118 Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar ,2 Wollenberg A. Mommaas M. Oppel T. Schottdorf E.M. Günther S. Moderer M. Expression and function of the mannose receptor CD206 on epidermal dendritic cells in inflammatory skin diseases. J. Invest. Dermatol. 2002; 118: 327-334https://doi.org/10.1046/j.0022-202x.2001.01665.x Abstract Full Text Full Text PDF PubMed Scopus (177) Google Scholar and, more recently, in uninflamed SSE. 3 Bertram K.M. Botting R.A. Baharlou H. Rhodes J.W. Rana H. Graham J.D. Patrick E. Fletcher J. Plasto T.M. Truong N.R. et al. Identification of HIV transmitting CD11c(+) human epidermal dendritic cells. Nat. Commun. 2019; 10: 2759https://doi.org/10.1038/s41467-019-10697-w Crossref PubMed Scopus (63) Google Scholar ,4 Pena-Cruz V. Agosto L.M. Akiyama H. Olson A. Moreau Y. Larrieux J.R. Henderson A. Gummuluru S. Sagar M. HIV-1 replicates and persists in vaginal epithelial dendritic cells. J. Clin. Invest. 2018; 128: 3439-3444https://doi.org/10.1172/jci98943 Crossref PubMed Scopus (0) Google Scholar In the October 2021 issue of Immunity, Liu et al. 5 Liu X. Zhu R. Luo Y. Wang S. Zhao Y. Qiu Z. Zhang Y. Liu X. Yao X. Li X. Li W. Distinct human Langerhans cell subsets orchestrate reciprocal functions and require different developmental regulation. Immunity. 2021; 54: 2305-2320.e11https://doi.org/10.1016/j.immuni.2021.08.012 Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar report four epidermal MNP subsets in human foreskin, termed LC1–4, further advancing our understanding of MNPs that inhabit the SSE. Here, we argue that all previous descriptions of SSE DCs, as well as LC2 described by Liu et al., are independent discoveries of the same cell, most likely a conventional DC2 (cDC2). Distinct human Langerhans cell subsets orchestrate reciprocal functions and require different developmental regulationLiu et al.ImmunitySeptember 10, 2021In BriefThe heterogeneity of Langerhans cells has long been considered. Liu et al. reveal four subpopulations of primary and HSC-derived Langerhans cells in human, which are phenotypically and functionally distinct and require different developmental regulation. Full-Text PDF Open ArchiveResponse to identifying the epidermal dendritic cell landscapeZhu et al.ImmunityMarch 14, 2023In BriefIn their letter to Immunity,1 Bertram et al. argue that a subset of Langerhans cells (LCs), LC2, which we recently defined,2 shares the same surface markers with epidermal CD11c+ dendritic cells (DCs) and is actually classical DC2 (cDC2). The authors summarized the previously reported markers of epidermal CD11c+ DC subsets and found that they were highly consistent with those of LC2.2 By analyzing the single-cell RNA sequencing (scRNA-seq) dataset from our work,2 Reynolds et al.,3 and their own bulk-population-sorted RNA-seq dataset (GSE166639), Bertram et al. Full-Text PDF