TY - JOUR
T1 - Niche rather than origin dysregulates mucosal Langerhans cells development in aged mice
AU - Horev, Yael
AU - Salameh, Rana
AU - Nassar, Maria
AU - Capucha, Tal
AU - Saba, Yasmin
AU - Barel, Or
AU - Zubeidat, Khaled
AU - Matanes, Daniela
AU - Leibovich, Amit
AU - Heyman, Oded
AU - Eli-Berchoer, Luba
AU - Hanhan, Salem
AU - Betser-Cohen, Gili
AU - Shapiro, Hagit
AU - Elinav, Eran
AU - Bercovier, Herve
AU - Wilensky, Asaf
AU - Hovav, Avi Hai
N1 - Publisher Copyright:
© 2020, Society for Mucosal Immunology.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85086389442&partnerID=8YFLogxK
U2 - 10.1038/s41385-020-0301-y
DO - 10.1038/s41385-020-0301-y
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C2 - 32457449
AN - SCOPUS:85086389442
SN - 1933-0219
VL - 13
SP - 767
EP - 776
JO - Mucosal Immunology
JF - Mucosal Immunology
IS - 5
ER -