Inflammatory diseases in skin have been shown to develop from aberrant interactions between skin immune cells and resident cells of the tissue. The innate immune arm, specifically macrophages have been shown to play critical role in driving the disease conditions since depletion of macrophages significantly reduces inflammatory burden in skin. While the crosstalk between macrophages and skin compartments has been studied largely at the level of cytokines and chemokines, much less has been understood at the level of metabolic crosstalk between macrophages and other skin compartments.
Metabolic factors have been shown to play supportive, instructive and permissive roles, essential for regulating fate decision in immune cells. Innate immune cells especially macrophages have been shown to exhibit remarkable functional and metabolic flexibility, capable of acquiring distinct M1 and M2 fates, in vitro. Interestingly, these M1 and M2 macrophages have been shown to be associated with distinct metabolic states where M1 macrophages have preferential dependence on glycolysis and M2 macrophages on tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS). While these metabolic pathways are well understood in vitro, much less is known about their states in tissues. In inflammatory skin conditions such as wounding, atopic dermatitis and psoriasis macrophages have been shown to acquire distinct functional states which exacerbate disease condition. Consistently, loss of macrophages lead to remarkable rescue of the diseased skin. However, much less is understood about how the metabolic crosstalk between different skin cells and macrophages bring about these switches.
In our work, we have used embryonic skin specific integrin b1 KO model of inflammation to investigate the metabolic crosstalk between skin compartments with macrophages to understand the initial event that drive inflammatory responses in skin. This allows us a rather simplified system since the embryonic skin lacks the adaptive immune arm.