@article {6679,
	title = {Metabolic rewiring of macrophages by epidermal-derived lactate promotes sterile inflammation in the murine skin.},
	journal = {EMBO J},
	volume = {43},
	year = {2024},
	month = {2024 Apr},
	pages = {1113-1134},
	abstract = {<p>Dysregulated macrophage responses and changes in tissue metabolism are hallmarks of chronic inflammation in the skin. However, the metabolic cues that direct and support macrophage functions in the skin are poorly understood. Here, we show that during sterile skin inflammation, the epidermis and macrophages uniquely depend on glycolysis and the TCA cycle, respectively. This compartmentalisation is initiated by ROS-induced HIF-1α stabilization leading to enhanced glycolysis in the epidermis. The end-product of glycolysis, lactate, is then exported by epithelial cells and utilized by the dermal macrophages to induce their M2-like fates through NF-κB pathway activation. In addition, we show that psoriatic skin disorder is also driven by such lactate metabolite-mediated crosstalk between the epidermis and macrophages. Notably, small-molecule inhibitors of lactate transport in this setting attenuate sterile inflammation and psoriasis disease burden, and suppress M2-like fate acquisition in dermal macrophages. Our study identifies an essential role for the metabolite lactate in regulating macrophage responses to inflammation, which may be effectively targeted to treat inflammatory skin disorders such as psoriasis.</p>
},
	keywords = {Animals, Inflammation, Lactic Acid, Macrophages, Mice, Psoriasis, Skin},
	issn = {1460-2075},
	doi = {10.1038/s44318-024-00039-y},
	author = {Ayyangar, Uttkarsh and Karkhanis, Aneesh and Tay, Heather and Afandi, Aliya Farissa Binte and Bhattacharjee, Oindrila and Ks, Lalitha and Lee, Sze Han and Chan, James and Raghavan, Srikala}
}
@article {1736,
	title = {Unraveling the ECM-Immune Cell Crosstalk in Skin Diseases.},
	journal = {Front Cell Dev Biol},
	volume = {7},
	year = {2019},
	month = {2019},
	pages = {68},
	abstract = {<p>The extracellular matrix (ECM) is a complex network of proteins and proteoglycans secreted by keratinocytes, fibroblasts and immune cells. The function of the skin ECM has expanded from being a scaffold that provides structural integrity, to a more dynamic entity that is constantly remodeled to maintain tissue homeostasis. The ECM functions as ligands for cell surface receptors such as integrins, dystroglycans, and toll-like receptors (TLRs) and regulate cellular signaling and immune cell dynamics. The ECM also acts as a sink for growth factors and cytokines, providing critical cues during epithelial morphogenesis. Dysregulation in the organization and deposition of ECMs lead to a plethora of pathophysiological conditions that are exacerbated by aberrant ECM-immune cell interactions. In this review, we focus on the interplay between ECM and immune cells in the context of skin diseases and also discuss state of the art therapies that target the key molecular players involved.</p>
},
	issn = {2296-634X},
	doi = {10.3389/fcell.2019.00068},
	author = {Bhattacharjee, Oindrila and Ayyangar, Uttkarsh and Kurbet, Ambika S and Ashok, Driti and Raghavan, Srikala}
}
