p16ink4a Positivity of Melanocytes in Non-Segmental Vitiligo

Abstract

Cellular senescence is induced in response to cellular stressors such as increased levels of reactive oxygen species. The chronic accumulation of senescent cells is currently recognized as a contributor to the pathologic processes of diverse degenerative diseases. Vitiligo is characterized by the disappearance of melanocytes driven by cellular stress within melanocytes and autoimmune processes. In this study, we examined p16INK4A positivity in the lesional and perilesional skin of 54 non-segmental vitiligo patients to explore cellular senescence in vitiligo. There were more p16INK4A-positive melanocytes in the perilesional vitiligo skin samples than in control samples. It was also found that p16INK4A immunoreactivity was not restricted to melanocytes but also existed in fibroblasts; the number of p16INK4A-positive fibroblasts was significantly increased in lesional skin compared to perilesional skin and normal controls. However, in the subgroup analysis of sun-exposed and non-exposed samples, this outcome was only found at sun-exposed sites, suggesting that fibroblast senescence is an epiphenomenon related to the loss of pigment in skin with vitiligo. In summary, exploring p16INK4A positivity in vitiligo revealed melanocyte senescence in perilesional skin, which may play a role in vitiligo pathogenesis.

NLRP1 inflammasome modulates senescence and senescence-associated secretory phenotype

“…Recent works showing that human NLRP1 senses ultraviolet B (UVB) damage in skin are consistent with our observations since UVB also induces senescence (30)(31)(32). Our findings were also consistent with the association of NLRP1 overexpression or gain-of-function mutations with the prevalence of skin diseases such as psoriasis, vitiligo, atopic dermatitis or hyperkeratosis (33) where senescence had been widely described (34,35).…”

Alterations of the pigmentation system in the aging process

“…The relevance of senescent fibroblasts in melasma has been very recently evidenced in vivo using radiofrequency therapy targeting dermis to reduce melasma pigmentation (Kim et al., 2019). In this case, the reduction of p16 positive fibroblasts and stimulation of collagen production drive a marked decrease in epidermal pigmentation (Lee et al., 2020). Additionally, factors other than sun exposure might also induce premature cellular aging in melasma, based on the overexpression of inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2), and interleukin 17 (IL‐17), which indicate a pro‐inflammatory state (Esposito et al, 2018).…”

Focus on the Contribution of Oxidative Stress in Skin Aging

“…Similarly, melasma (melanotic hypermelanosis) is a chronic relapsing hyperpigmentary disease presenting evidence of oxidative stress, subclinical inflammation, and several senescence markers [ 322 , 323 ]. In melasma, senescent-associated markers have been documented exclusively in disease-involved skin areas, whereas in vitiligo patients, the presence of the senescence feature has been delineated as a diffuse trait of the epidermis and the dermis in both lesional and non-lesional skin [ 238 , 281 , 324 ], suggesting an intrinsic susceptibility to premature senescence of vitiligo patients. Accordingly, for vitiligo, disease risk has been partially attributed to polygenic variants [ 325 ].…”