Niche rather than origin dysregulates mucosal Langerhans cells development in aged mice

Yael Horev, Rana Salameh, Maria Nassar, Tal Capucha, Yasmin Saba, Or Barel, Khaled Zubeidat, Daniela Matanes, Amit Leibovich, Oded Heyman, Luba Eli-Berchoer, Salem Hanhan, Gili Betser-Cohen, Hagit Shapiro, Eran Elinav, Herve Bercovier, Asaf Wilensky*, Avi Hai Hovav*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Unlike epidermal Langerhans cells (LCs) that originate from embryonic precursors and are self-renewed locally, mucosal LCs arise and are replaced by circulating bone marrow (BM) precursors throughout life. While the unique lifecycle of epidermal LCs is associated with an age-dependent decrease in their numbers, whether and how aging has an impact on mucosal LCs remains unclear. Focusing on gingival LCs we found that mucosal LCs are reduced with age but exhibit altered morphology with that observed in aged epidermal LCs. The reduction of gingival but not epidermal LCs in aged mice was microbiota-dependent; nevertheless, the impact of the microbiota on gingival LCs was indirect. We next compared the ability of young and aged BM precursors to differentiate to mucosal LCs. Mixed BM chimeras, as well as differentiation cultures, demonstrated that aged BM has intact if not superior capacity to differentiate into LCs than young BM. This was in line with the higher percentages of mucosal LC precursors, pre-DCs, and monocytes, detected in aged BM. These findings suggest that while aging is associated with reduced LC numbers, the niche rather than the origin controls this process in mucosal barriers.

Original languageEnglish
Pages (from-to)767-776
Number of pages10
JournalMucosal Immunology
Volume13
Issue number5
DOIs
StatePublished - 1 Sep 2020

Bibliographical note

Publisher Copyright:
© 2020, Society for Mucosal Immunology.

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