Defensin 4

Multipotent stem cells have paved the way for new applications and deeper understanding in regenerative medicine and the pathophysiology of aging. During skin aging, cumulative photodamage, exhaustion of endogenous stem cell populations, mechanical stress, and increased fibrosis lead to skin with decreased epidermal thickness and compromised dermal integrity. Specific stem cells in the hair follicle create new keratinocytes after activation by defensin peptides, released by neutrophils during wounding. Studies pertaining to defensin peptides' efficacy on skin aging have been published, highlighting their potential as a new therapy for skin rejuvenation.

β-Defensin (BD) is an important first line innate defense molecule with potent antimicrobial and immunomodulatory activities in fish. The signatures of β-defensins are the presence of a net cationic charge and three intramolecular disulfide bonds mediated by six conserved cysteines. It consists of three exons and two introns. The signal peptide is usually conserved and sequence divergence is mostly seen in mature peptide region. The diverse amino acid sequences of matured peptide contribute to a strong positive selection and broad-spectrum antimicrobial activity. It is constitutively expressed in both mucosal as well as systemic sites. Increased expression of β-defensin was mostly reported in bacterial and viral infections in fish. Its role during parasitic and fungal infections is yet to be investigated. β-Defensin isoforms such as BD-1, BD-2, BD-3, BD-4 and BD-5 can be witnessed even in early developmental days to different pathogenic exposure in fish. β-Defensins possess adjuvant properties to enhance antigen-specific immunity promoting both cellular and humoral immune response. It significantly reduces/increases bacterial colonization or viral copy numbers when overexpressed/knockdown. Based on its chemotactic and activating potentials, it can contribute to both innate and adaptive immune responses. With mediated expression, it can also control inflammation. It is potent governing resistance in early developmental days as well. Its expression in pituitary and testis suggests its participation in reproduction and endocrine regulation in fish. Overall, β-defensins is an important member of antimicrobial peptides (AMPs) with multifunctional role in general homeostasis and to pathogen exposure possessing tremendous therapeutic approaches.

Human β-defensin-3 (hBD-3) exhibits antimicrobial and immunomodulatory activities; however, its contribution to autophagy regulation remains unclear, and the role of autophagy in the regulation of the epidermal barrier in atopic dermatitis (AD) is poorly understood. Here, keratinocyte autophagy was restrained in the skin lesions of patients with AD and murine models of AD. Interestingly, hBD-3 alleviated the IL-4- and IL-13-mediated impairment of the tight junction (TJ) barrier through keratinocyte autophagy activation, which involved aryl hydrocarbon receptor (AhR) signaling. While autophagy deficiency impaired the epidermal barrier and exacerbated inflammation, hBD-3 attenuated skin inflammation and enhanced the TJ barrier in AD. Importantly, hBD-3-mediated improvement of the TJ barrier was abolished in autophagy-deficient AD mice and in AhR-suppressed AD mice, suggesting a role for hBD-3-mediated autophagy in the regulation of the epidermal barrier and inflammation in AD. Thus, autophagy contributes to the pathogenesis of AD, and hBD-3 could be used for therapeutic purposes.