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.