Phenotype, Function, and Mobilization of 6-Sulfo LacNAc-Expressing Monocytes in Atopic Dermatitis

Area of Science:

• Immunology
• Dermatology
• Cell Biology

Background:

• Mononuclear phagocytes (MPs) play a key role in regulating immune responses in atopic dermatitis (AD).
• 6-sulfo LacNAc-expressing monocytes (slanMo) were previously identified as cytokine-producing cells in psoriasis.
• Cytokines like IFN-γ, IL-17, and IL-22 are elevated in AD and decrease with treatment, including dupilumab.

Purpose of the Study:

• To investigate the specific role of slanMo in the pathogenesis of atopic dermatitis (AD).
• To characterize slanMo populations in AD skin lesions and blood compared to other myeloid cells.

Main Methods:

• Analysis of slanMo numbers and surface marker expression (FcɛRI, CD1a, CD14, CD163, CD86) in AD skin lesions and blood.
• Quantification of cytokine production (IL-12, TNF-α) by slanMo, CD14+ monocytes, and myeloid dendritic cells from AD patients and healthy controls.
• Assessment of slanMo mobilization following experimentally induced mental stress.

Main Results:

• Increased numbers of slanMo were observed in AD skin lesions compared to controls.
• AD slanMo expressed higher levels of CD86 and produced more IL-12 and TNF-α than other myeloid cells, despite lacking FcɛRI, CD1a, CD14, and CD163.
• Mental stress rapidly mobilized slanMo, which maintained their high TNF-α production capacity.
• Unlike CD14+ monocytes, slanMo cytokine production did not differ between AD patients and healthy controls.

Conclusions:

• SlanMo represent a distinct inflammatory cell population within AD skin lesions.
• SlanMo function as proinflammatory cells in the blood of AD patients.
• SlanMo emerge as a promising cellular target for future therapeutic interventions in AD.