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

Area of Science:

• Immunology
• Cell Biology
• Aging Research

Background:

• Epidermal Langerhans cells (LCs) originate embryonically and self-renew.
• Mucosal LCs are continuously replaced by bone marrow (BM) precursors.
• The impact of aging on mucosal LC populations is largely unknown.

Purpose of the Study:

• To investigate the effect of aging on gingival LCs, a mucosal LC population.
• To determine if aging affects the bone marrow precursor capacity to generate mucosal LCs.
• To explore the role of microbiota in age-related changes of mucosal LCs.

Main Methods:

• Comparative analysis of gingival and epidermal LCs in young and aged mice.
• Microbiota depletion experiments.
• Bone marrow chimera generation and in vitro differentiation cultures.
• Flow cytometry to quantify precursor populations.

Main Results:

• Aged mice showed reduced numbers of gingival LCs with altered morphology.
• Gingival LC reduction in aged mice was microbiota-dependent but indirectly mediated.
• Aged bone marrow precursors exhibited intact or superior capacity to differentiate into mucosal LCs compared to young precursors.
• Increased percentages of mucosal LC precursors, pre-dendritic cells, and monocytes were found in aged bone marrow.

Conclusions:

• Aging is associated with a decline in mucosal LC numbers, particularly in the gingiva.
• The local microenvironment (niche) appears to be the primary regulator of age-related mucosal LC reduction, rather than intrinsic defects in bone marrow precursors.
• These findings highlight distinct aging dynamics between epidermal and mucosal immune cells and identify the niche as a critical factor in mucosal barrier immunity during aging.