Fig. 1

Immunologic modulation of filaggrin (FLG) in the development of atopic dermatitis. Decreased FLG exacerbates skin inflammation in many ways. Th2 phenotype skewing occurs because of barrier disruption and keratinocyte injuries that stimulate thymic stromal lymphopoietin (TSLP), Th2, and eosinophil-recruiting chemokines together with IL-33 and IL-25 released from keratinocytes. Moreover, the loss of the acid mantle in the epidermis also promotes TSLP secretion via protease-activated receptor type 2 (PAR-2) activation by increased serine proteases. Enhanced allergen penetration and microbial colonization activate inflammasomes and the Th17 pathway that complicate the pathogenesis of AD in a later state