Langerhans cells shape postnatal oral homeostasis in a mechanical-force-dependent but microbiota and IL17-independent manner

Yasmin Jaber, Yasmine Netanely, Reem Naamneh, Or Saar, Khaled Zubeidat, Yasmin Saba, Olga Georgiev, Paz Kles, Or Barel, Yael Horev, Omri Yosef, Luba Eli-Berchoer, Chen Nadler, Gili Betser-Cohen, Hagit Shapiro, Eran Elinav, Asaf Wilensky and Avi-Hai Hovav ()
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Yasmin Jaber: Hebrew University
Yasmine Netanely: Hebrew University
Reem Naamneh: Hebrew University
Or Saar: Hebrew University, Jerusalem, Israel; Department of Periodontology, Hadassah Medical Center
Khaled Zubeidat: Hebrew University
Yasmin Saba: Hebrew University
Olga Georgiev: Hebrew University
Paz Kles: Hebrew University, Jerusalem, Israel; Department of Periodontology, Hadassah Medical Center
Or Barel: Hebrew University
Yael Horev: Hebrew University, Jerusalem, Israel; Department of Periodontology, Hadassah Medical Center
Omri Yosef: Hebrew University
Luba Eli-Berchoer: Hebrew University
Chen Nadler: Faculty of Dental Medicine, Hebrew University
Gili Betser-Cohen: Division of Identification and Forensic Science, Police National HQ
Hagit Shapiro: System Immunology Department, Weizmann Institute of Science
Eran Elinav: System Immunology Department, Weizmann Institute of Science
Asaf Wilensky: Hebrew University, Jerusalem, Israel; Department of Periodontology, Hadassah Medical Center
Avi-Hai Hovav: Hebrew University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract The postnatal interaction between microbiota and the immune system establishes lifelong homeostasis at mucosal epithelial barriers, however, the barrier-specific physiological activities that drive the equilibrium are hardly known. During weaning, the oral epithelium, which is monitored by Langerhans cells (LC), is challenged by the development of a microbial plaque and the initiation of masticatory forces capable of damaging the epithelium. Here we show that microbial colonization following birth facilitates the differentiation of oral LCs, setting the stage for the weaning period, in which adaptive immunity develops. Despite the presence of the challenging microbial plaque, LCs mainly respond to masticatory mechanical forces, inducing adaptive immunity, to maintain epithelial integrity that is also associated with naturally occurring alveolar bone loss. Mechanistically, masticatory forces induce the migration of LCs to the lymph nodes, and in return, LCs support the development of immunity to maintain epithelial integrity in a microbiota-independent manner. Unlike in adult life, this bone loss is IL-17-independent, suggesting that the establishment of oral mucosal homeostasis after birth and its maintenance in adult life involve distinct mechanisms.

Date: 2023
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DOI: 10.1038/s41467-023-41409-0

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