**5. Leptin as an immune modulator**

Despite nutritional regulation, leptin has gained more attention for its pivotal role in inflammation. The innate immune system plays a major role in the regulation of leptin production. Leptin responds to immune cells and its receptors, expressed by most cells, and activates pro-inflammatory features in the host [39]. Leptin plays an essential role in T cell development, and leptin deficiency directly impacts the levels of circulating T cells [40]. Many studies supported the role of leptin in immunity modulation and mentioned the signaling pathways related to the notion [39, 41, 42]. Leptin could accelerate the proliferation process in native CD4+ T cells and favored by reducing the levels of IFN from T cells [43, 44]. During the wound healing process, leptin activates both inflammatory and proliferative phases in favor of tissue repair [45]. The increased plasma leptin level acts as an indicator of leptin-induced inflammatory response at the injury site. These exciting features of leptin gained attention as a pro-angiogenic molecule in ischemic tissues [46]. Leptin induces monocyte chemoattractant protein1 (MCP1) expression [47].

Leptin plays a vital role in producing GM-CSF and G-CSF and activating hematopoietic cells in humans [48]. In animal models, up-regulation of leptin has been found in acute inflammation states. But, experimental evidence from rodents does not match with human studies [49]. Leptin plays a significant role in basophils and eosinophils functions and acts as a chemoattractant [50]. Leptin is abnormally expressed in autoimmune diseases, particularly in skin disorders [51]. Obesity decorates skin normal physiology such as keratosis pilaris, tags, and striae diseases and increases the levels of pro-inflammatory cytokines and adipokines, including leptin [52, 53]. In the event of inflammation, leptin increases the release of Nitric Oxide and activates the macrophages and neutrophils, and increases natural killer cells' activity (NK) [54]. Leptin up-regulates the cytokines production and phagocytic function in obese conditions [55]. It balances monocytes and activations markers and directly involves in interleukin1 and cyclooxygenase expression [56]. One of the prominent roles of leptin pertains to maintaining the balance between the immune system and metabolism regulation. Under malnutrition state, leptin acts as an immunosuppressive factor [42].
