Langerin is not restricted to Langerhans cells, but expressed at low levels by CD1c + dendritic cells and is inducible by TGFβ in humans.
Langerin is a C-type lectin expressed at high level by LCs of the epidermis. Langerin is also expressed by CD8 +/CD103 + XCR1 + cross-presenting DCs of mice but is not found on the homologous human CD141 high XCR1 + myeloid DC. Here, we show that langerin is expressed at a low level on DCs isolated from dermis, lung, liver, and lymphoid tissue and that langerin + DCs are closely related to CD1c + myeloid DCs. They are distinguishable from LCs by the level of expression of CD1a, EpCAM, CD11b, CD11c, CD13, and CD33 and are found in tissues and tissue-draining LNs devoid of LCs. They are unrelated to CD141 high XCR1 + myeloid DCs, lacking the characteristic expression profile of cross-presenting DCs, conserved between mammalian species. Stem cell transplantation and DC deficiency models confirm that dermal langerin + DCs have an independent homeostasis to LCs. Langerin is not expressed by freshly isolated CD1c + blood DCs but is rapidly induced on CD1c + DCs by serum or TGF- β via an ALK-3-dependent pathway. These results show that langerin is expressed outside of the LC compartment of humans and highlight a species difference: langerin is expressed by the XCR1 + "DC1" population of mice but is restricted to the CD1c + "DC2" population of humans (homologous to CD11b + DCs in the mouse).