Response to identifying the epidermal dendritic cell landscape

In their letter to Immunity, 1 Bertram K.M. O’Neil T.R. Vine E.E. Baharlou H. Cunningham A.L. Harman A.N. Defining the landscape of human epidermal mononuclear phagocytes. Immunity. 2023; 56: 459-460https://doi.org/10.1016/j.immuni.2023.02.001 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Bertram et al. argue that a subset of Langerhans cells (LCs), LC2, which we recently defined, 2 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 (26) Google Scholar 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 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 (26) Google Scholar By analyzing the single-cell RNA sequencing (scRNA-seq) dataset from our work, 2 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 (26) Google Scholar Reynolds et al., 3 Reynolds G. Vegh P. Fletcher J. Poyner E.F.M. Stephenson E. Goh I. Botting R.A. Huang N. Olabi B. Dubois A. et al. Developmental cell programs are co-opted in inflammatory skin disease. Science. 2021; 371: eaba6500https://doi.org/10.1126/science.aba6500 Crossref PubMed Scopus (163) Google Scholar and their own bulk-population-sorted RNA-seq dataset (GSE166639), Bertram et al. demonstrated that DCs were present in the epidermis, and LC2 or CD11c+ cells more closely resembled dermal cDC2 than LCs. 1 Bertram K.M. O’Neil T.R. Vine E.E. Baharlou H. Cunningham A.L. Harman A.N. Defining the landscape of human epidermal mononuclear phagocytes. Immunity. 2023; 56: 459-460https://doi.org/10.1016/j.immuni.2023.02.001 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar They further proposed that LC2, epidermal CD11c+ DCs, inflammatory dendritic epidermal cells (IDECs), and vaginal DECs (VDECs) were independent identifications of the same cell population using different gate strategies. 1 Bertram K.M. O’Neil T.R. Vine E.E. Baharlou H. Cunningham A.L. Harman A.N. Defining the landscape of human epidermal mononuclear phagocytes. Immunity. 2023; 56: 459-460https://doi.org/10.1016/j.immuni.2023.02.001 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar We appreciate the concerns and agree with the authors that there is substantial overlap in gene expression between epidermal CD11c+ DCs and LC2, particularly for surface markers. However, LC2 are not only different from cDC2 in phenotype but also demonstrate distinct features in transcription factors (TFs), function, and ontogeny that closely align with those of LCs. Defining the landscape of human epidermal mononuclear phagocytesBertram et al.ImmunityMarch 14, 2023In BriefThe 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 SSE1,2 and, more recently, in uninflamed SSE.3,4 In the October 2021 issue of Immunity, Liu et al. Full-Text PDF