Distinct Murine Mucosal Langerhans Cell Subsets Develop from Pre-dendritic Cells and Monocytes

Area of Science:

• Immunology
• Developmental Biology
• Epithelial Biology

Background:

• Langerhans cells (LCs) are critical immune cells in mucosal epithelia, a primary pathogen entry site.
• The developmental origins of mucosal LCs remain poorly understood, contrasting with skin LCs.

Purpose of the Study:

• To elucidate the ontogeny of oral mucosal Langerhans cells (LCs).
• To compare the origins and characteristics of oral mucosal LCs with skin LCs and other dendritic cells (DCs).

Main Methods:

• Analysis of precursor origins using radioresistance assays.
• Flow cytometry to identify distinct LC subsets (CD103(+) and CD11b(+)).
• Transcriptomic analysis and functional immunological assays.

Main Results:

• Oral mucosal LCs derive from circulating, radiosensitive precursors, unlike radioresistant embryonic precursors for skin LCs.
• Oral mucosal LCs comprise CD103(+) and CD11b(+) subsets, originating from pre-dendritic cells (pre-DCs) and monocytic precursors.
• Oral LCs exhibit transcriptomic and functional similarities to skin LCs, supporting their classification as genuine LCs.

Conclusions:

• Murine Langerhans cells differentiate from at least three distinct precursors (embryonic, pre-DC, monocytic) in a tissue-dependent manner.
• Oral mucosal LCs are confirmed as authentic LCs, despite their unique ontogenetic pathway compared to skin LCs.