4. SAT in autoimmune diseases
SAT is recognized as an active contributor to immune regulation and modulation. Dysregulation in resident macrophages, T-regs and other immune cells within SAT can lead to excessive cytokine production and autoimmune diseases (113-115). This disrupted balance can be originated within the adipocytes in SAT secreting various pro-inflammatory cytokines and chemokines, creating an environment conductive to immune dysregulation. Furthermore, imbalances in adipokine levels may contribute to the dysregulation of immune responses and exacerbate autoimmune conditions (116, 117). A focused investigation into the specific roles of resident T-regs and macrophages along with exploration of the involvement of cytokines and adipokines in this dysregulation is crucial for understanding the pathways leading to autoimmune diseases.
MHC-like cell surface CD1 family proteins have the capacity to present lipid antigens (118, 119). Several studies suggest a possible role of AT-derived CD1-presented lipid antigens in autoimmunity. For example, adipocytes from obese mice express CD1d, contributing to the induction of an autoreactive immune response (120). A better understanding of the interplay between adipocytes, lipid autoantigens, and CD1 presentation will elucidate a new, and potentially targetable, pathway in autoimmunity. In healthy human skin, there appears to be competition between permissive and blocking lipids for presentation by CD1a, the balance of which can modulate T cell responses (121). Specifically, presentation of very long chain FAs, such as 42:2 sphingomyelin lipids, by CD1a has been observed to impede the engagement of CD1a-directed autoreactive T-cells (122). A disruption of this balance may favor the development of autoimmune processes. Therefore, it is intriguing to explore the CD1a-related functions and pathways as potential targets in the prevention and treatment of autoimmune conditions.