Seborrheic dermatitis (SD) is a chronic-relapsing inflammatory skin disease with three incidence peaks: within the first three months of life, during puberty, and in adulthood (40-60 years). Its etiology is multifactorial and can be attributed to: (I) excessive sebum production by the sebaceous gland (SG) and alterations in its composition, creating an environment favorable to the growth of Malassezia; (II) activation of SG metabolism and its secretory activity by Malassezia, with the release of irritating saturated and unsaturated fatty acids; (III) impaired immune system function, leading to the induction of keratinocyte activation and differentiation; and (IV) disruption of the skin barrier, responsible for clinical manifestations such as erythema, itching, and scaling.
Studies focusing on the presence of immunocompetent cells at barrier sites (intestinal lamina propria, lungs, and skin) have shown that, at the intestinal level, diet and metabolism can influence the phenotype of Th17 lymphocytes. Indeed, dietary enrichment in short-chain fatty acids can promote differentiation toward Treg, whereas the habitual dietary intake of long-chain fatty acids, as well as higher salt consumption, is associated with an increased number of lymphocytes with a Th17 functional profile, and thus with a state of autoimmunity. Barrier sites are typically rich in TRM (tissue-resident memory T) cells, which display site-specific functional profiles tailored to local homing requirements. In the skin, TRM are characterized by high expression of CCR4, CCR10, CXCR4, GATA6, and BCL6. In contrast, the TEM (T effector memory) and TEMRA (terminally differentiated effector memory) compartments appear to share a functional profile across different barrier sites and peripheral tissues.
However, the classification of barrier-site T cells into Th1, Th17, and Th2 subtypes should be viewed in a nuanced way-as an expression of functional characteristics rather than the final outcome of a maturation and differentiation process. In particular, Th17 lymphocytes can modify their functional phenotype, exhibiting distinct transcriptional profiles associated with either homeostatic or pathogenic potential, suggesting that these should be considered tissue-dependent functional states rather than different cell types. Th17 lymphocytes are associated with secretion of IL-17A, IL-17F, and IL-22, and depend on the RORγt-dependent signaling pathway, while TGF-β and IL-6 are required for their generation from naïve T lymphocytes. Studies on the involvement of immune components in the etiopathogenesis of SD have so far focused on the skin, where a role for γδ T cells has been observed, with secretion of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, β-defensins-likely related to the maturation of dendritic cells induced by sebaceous lipids and the subsequent induction of the NLRP3 inflammasome.
Malassezia itself can induce the release of IL-1β in vitro by dendritic cells obtained from peripheral blood.
No studies are currently available on the possible involvement, in terms of functional modulation, of peripheral blood lymphomonocytes in the pathogenesis of SD.
Likewise, despite known dietary influences on Th17 cell function at barrier sites such as the intestinal mucosa, data are lacking regarding the role of diet and lifestyle in seborrheic dermatitis.
