Conclusion and clinical perspectives:
There is a growing body of evidence highlighting
the intricate and crucial immune
functions of AT (25-27). Understanding the specific contributions of SAT
in both homeostatic and pathological states remains a central challenge.
Key questions need to be addressed to unravel immune loops between SAT
and the skin or other organ systems.
Primarily, there is a need for a better understanding of the
immunological reservoir within SAT in humans under homeostatic
conditions. This necessitates a through characterization and functional
exploration of both cellular (leukocytic and non-leukocytic) and
molecular immune components within SAT. Also, characterizing the
distinctions in SAT resident immune cells across various topographical
locations of the body is crucial for elucidating their impact on skin
homeostasis.
A pivotal aspect of this exploration is deciphering antigen presentation
in SAT, including the identification of antigen-presenting cells (APC)
and the nature of presented antigens. While AT-resident macrophages are
the primary APC population in mice (173), obesity models have shown
adipocytes expressing major histocompatibility complex II and activating
CD4+ T-cells (174-176). The involvement of APCs beyond macrophages in
humans remains unclear, necessitating further research to develop
novel therapeutic strategies for
SAT-based immune diseases.
In addition to comprehending immune dynamics under homeostatic
conditions, it is crucial to delve into the pathomechanisms of SAT
inflammation, using panniculitis as a representative model. The
investigation of “immune loops” connecting SAT with the superficial
skin layers or the systemic level, as observed in psoriasis and
potentially other inflammatory conditions holds significant importance
(177). Moreover, understanding the impact of SAT-based processes on both
inflammatory and neoplastic conditions, as illustrated by data from
breast cancer and SPTLC, is crucial (178-180). Additionally, the
potential contribution of leaky barriers to increased inflammation in
adipose tissue (181), along with the migration of proinflammatory cells
(DC, Mac, CD1) from the adipose tissue to inflammatory organs, warrants
exploration.
To investigate specific antigens and signaling pathways, and cell-cell
interactions in various contexts, the development of full thickness skin
models, comprising SAT, dermis and epidermis is warranted. A detailed
understanding of SAT-based pathomechanisms facilitates the development
of small molecule inhibitors targeting immunogenic antigens to mitigate
inflammatory-driven complications.
Moreover, considering the
potential impact of obesity on these conditions, modulating SAT immune
responses emerges as a promising avenue for developing targeted
therapies against cutaneous / systemic immune-related diseases and
obesity (Fig 7).
Table 1: Secreted antimicrobial molecules, adipokines and cytokines in
obese adipose tissue