[Effect of CD4⁺T cell-specific methyltransferase-like 3 gene knockout on calcipotriol-induced atopic dermatitis in...

Objective: To investigate the regulatory role of methyltransferase-like protein 3 (Mettl3) within CD4⁺T cells in a mouse model of atopic dermatitis (AD) induced by calcipotriol (MC903). Methods: The C57BL/6 mouse model with CD4⁺T cell-specific Mettl3 knockout (Mettl3^-/-) was constructed (cKO group, n=4), with Mettl3^flox/flox mice lacking CD4-Cre recombinase serving as the control group (WT group, n=4). An AD-like dermatitis model was induced by topical application of MC903 to the ventral side of the right ear. The characteristics of AD-like dermatitis were assessed based on erythema and scaling at the lesion site, epidermal and dermal thickness, and the scoring of AD (SCORAD). The mRNA expression levels of key cytokines [interleukin (IL)-4, IL-10, etc.] and filaggrin (FLG) in the skin lesions, as well as the proportions of CD4⁺T cell subsets in the draining lymph nodes, were measured. Results: In the MC903-induced AD-like skin inflammation model, compared with the WT group, the cKO group exhibited less severe AD-like skin lesions, reduced skin thickening, decreased epidermal thickness [(45.4±16.3) μm vs (59.6±2.9) μm], less edema, and lower SCORAD scores. The mRNA expression level of IL-4 in the skin lesions was lower [(0.7±0.1) vs (1.0±0.1)], while the mRNA expression levels of FLG and IL-10 were higher [(2.7±1.3) vs (1.0±0.1) and (1.4±0.3) vs (1.0±0.1), respectively] (all P<0.05). The proportion of regulatory T cells in the draining lymph nodes was significantly higher in the cKO group [(5.7%±1.3%) vs (2.4%± 0.3%), P<0.05]. The proportion of T helper 2 cells (Th2) was lower, with no significant difference [(0.7%±0.2%) vs (0.8%±0.7%), P>0.05]. Conclusion: CD4⁺T cell-specific deletion of Mettl3 modulates IL-4, IL-10, and FLG expression, alters the Th2/Treg cell ratio, and thereby attenuates MC903-induced AD-like dermatitis in mice.