Immunization with a Pneumococcal pep27 Mutant Strain Alleviates Atopic Dermatitis through the Upregulation of Regulatory T-Cell Activity and Epithelial Barrier Function and Suppressing TSLP Expression.

Atopic dermatitis (AD) is an inflammatory disease driven in part by type 2 helper T (Th2) cytokines and skin barrier disruption alleviating the entry of allergens. Thymic stromal lymphopoietin (TSLP), an epithelial cell‒derived cytokine, is known to aggravate AD symptoms by activating Th2. In addition, regulatory T cells (Tregs) inhibit inflammatory cells such as Th2. However, the relationship between TSLP and Tregs in AD is unclear. A murine dermatitis model was induced by applying oxazolone to the ear skin of mice. Prophylactic and therapeutic responses were analyzed by immunizing mice intranasally with a pneumococcal pep27 mutant (Δpep27 mutant), attenuated strain by reducing the virulence of a pathogen. Intranasal immunization with a pneumococcal pep27 mutant could elicit anti-inflammatory Treg-relevant factors and epithelial barrier genes (loricrin, involucrin, filaggrin, and small proline-rich repeat proteins). Thus, pneumococcal pep27-mutant immunization suppressed epidermal collapse, IgE, TSLP, and upregulation of Th2 expression by upregulating Treg activity. In contrast, Treg inhibition aggravated AD symptoms through the upregulation of TSLP and Th2 and the repression of epithelial barrier function compared with that of the noninhibited pneumococcal Δpep27-mutant group. Taken together, immunization with pneumococcal Δpep27 mutant upregulated Treg and epithelial barrier function and inhibited TSLP and Th2 to relieve AD symptoms.