%0 Journal Article %J Front Cell Dev Biol %D 2019 %T Unraveling the ECM-Immune Cell Crosstalk in Skin Diseases. %A Bhattacharjee, Oindrila %A Ayyangar, Uttkarsh %A Kurbet, Ambika S %A Ashok, Driti %A Raghavan, Srikala %X

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.

%B Front Cell Dev Biol %V 7 %P 68 %8 2019 %G eng %R 10.3389/fcell.2019.00068 %0 Journal Article %J Cell Rep %D 2016 %T Sterile Inflammation Enhances ECM Degradation in Integrin β1 KO Embryonic Skin. %A Kurbet, Ambika S %A Hegde, Samarth %A Bhattacharjee, Oindrila %A Marepally, Srujan %A Vemula, Praveen K %A Raghavan, Srikala %K Animals %K Extracellular Matrix %K Inflammation %K Integrin beta1 %K Macrophages %K Mice %K Mice, Knockout %K Signal Transduction %K Skin %X

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 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.

%B Cell Rep %V 16 %P 3334-3347 %8 2016 09 20 %G eng %N 12 %R 10.1016/j.celrep.2016.08.062