Abstract
The endoplasmic reticulum-associated protein reticulon 1A (RTN1A) is primarily expressed in neuronal tissues but was recently identified also specifically in cells of the dendritic cell (DC) lineage, including epidermal Langerhans cells (LCs) and dermal DCs in human skin. In this study, we found that in mice major histocompatibility complex class II (MHCII)+CD207+ LCs but not dermal DCs express RTN1A. Further, RTN1A expression was identified in CD45+MHCII+CD207+ cells of the lymph node and spleen but not in the thymus. Of note, RTN1A was expressed in CD207low LCs in adult skin as well as emigrated LCs and DCs in lymph nodes and marginally in CD207hi cells. Ontogeny studies revealed that RTN1A expression occurred before the appearance of the LC markers MHCII and CD207 in LC precursors, while dermal DC and T cell precursors remained negative during skin development. Analogous to the expression of RTN1A in neural tissue, we identified expression of RTN1A in skin nerves. Immunostaining revealed co-localization of RTN1A with nerve neurofilaments only in fetal but not in newborn or adult dermis. Our findings suggest that RTN1A might be involved in the LC differentiation process given its early expression in LC precursors and stable expression onward. Further analysis of the RTN1A expression pattern will enable the elucidation of the functional roles of RTN1A in both the immune and the nervous system of the skin.
Highlights
RESULTSThe endoplasmic reticulum (ER) is the largest and most spatial organelle in mammalian cells (Baumann and Walz, 2001) comprising a nuclear envelope and the peripheral ER with rough and smooth membrane domains (Shibata et al, 2006)
We have analyzed the expression of reticulon 1A (RTN1A) in mouse skin and murine lymphoid organs, an endoplasmic reticulum protein, which was previously considered to be specific for nerve cells
We found that the expression of RTN1A in mouse skin showed considerable differences to that in human skin as it was restricted to Langerhans cells (LCs) but absent from other skin cells
Summary
The endoplasmic reticulum (ER) is the largest and most spatial organelle in mammalian cells (Baumann and Walz, 2001) comprising a nuclear envelope and the peripheral ER with rough and smooth membrane domains (Shibata et al, 2006). Single cell transcriptome analysis of mouse epidermis showed RTN1 gene expression exclusively in LCs, and that its expression was lower compared to that of typical LC markers such as MHCII and CD207 (Figure 1C and Supplementary Figures 2A–E). In situ staining revealed that the majority of MHCII+ and CD11c+ cells in the sinus co-expressed RTN1A+ (Figure 4C, upper panel), again confirming mRNA data for RTN1 expression in DCs. investigations of LCs with the CD207 marker, three populations were found: CD207+RTN1A+, CD207−RTN1A+, and CD207+RTN1A− cells in the lymph node sinus (Figure 4C, lower panel). Investigations of LCs with the CD207 marker, three populations were found: CD207+RTN1A+, CD207−RTN1A+, and CD207+RTN1A− cells in the lymph node sinus (Figure 4C, lower panel) This observation was substantiated by flow cytometry showing that 31% of CD207lo cells expressed RTN1A while CD207hi cells were RTN1A−.
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