@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 {1168,
	title = {Sterile Inflammation Enhances ECM Degradation in Integrin β1 KO Embryonic Skin.},
	journal = {Cell Rep},
	volume = {16},
	year = {2016},
	month = {2016 09 20},
	pages = {3334-3347},
	abstract = {<p>Epidermal knockout of integrin β1 results in complete disorganization of the basement membrane (BM), resulting in neonatal lethality. Here, we report that this disorganization is exacerbated by an early\&nbsp;embryonic inflammatory response involving the recruitment of tissue-resident and monocyte-derived macrophages to the dermal-epidermal junction, associated with increased matrix metalloproteinase activity. Remarkably, the skin barrier in the integrin β1 knockout animals is intact, suggesting that this inflammatory response is initiated in a sterile environment. We demonstrate that the molecular mechanism involves de novo expression of integrin αvβ6 in the basal epidermal cells, which activates a TGF-β1 driven inflammatory cascade resulting in upregulation of dermal NF-κB in a Tenascin C-dependent manner. Importantly, treatment of β1 KO embryos in utero with small molecule inhibitors of TGF-βR1 and NF-κB results in marked rescue of the BM defects and amelioration of immune response, revealing an unconventional immuno-protective role for integrin β1 during BM remodeling.</p>
},
	keywords = {Animals, Extracellular Matrix, Inflammation, Integrin beta1, Macrophages, Mice, Mice, Knockout, Signal Transduction, Skin},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2016.08.062},
	author = {Kurbet, Ambika S and Hegde, Samarth and Bhattacharjee, Oindrila and Marepally, Srujan and Vemula, Praveen K and Raghavan, Srikala}
}
