Ts/CRISPR-associated protein) immune function in bacteria and archaea from foreign DNA attacks107. Of note, the class defining criteria of being able to present antigens by way of MHC II is not quite restricted. It was not too long ago reported working with new single-cell RNA sequencing method to separate antigenpresenting MHC II-high dendritic cell (DC) population from inflammatory functionhigh DC population108, suggesting that not all the DC have high antigen presenting capacity. Other current reports demonstrated that some professional innate immune cells including B cells, macrophages, all-natural killer cells (NK), monocytes, plasmacytoid dendritic cells (pDC), DC1 and DC2 have 1,300 innate immune gene expression differences, suggesting huge heterogeneities109, 110. Consequently, it might not be optimal to work with antigen-presenting capacity111, 112 as the vital criterion for judging the innate immune function of ECs. ECs have classical DAMPs sensing systems. Classic innate immune cells that patrol the blood, like DCs, and Ly6Clow monocytes24, 113, is equipped having a series of PAMPs receptors such as Tolllike receptors (TLRs)114 and NOD-like receptors (NLRs)52, 115. TLRs, NLRs, retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLRs), absent in melanoma two (AIM2)-like receptors (ALRs) and C-type lectin receptors (CLRs) are pattern recognition receptors (PRRs). These receptors are part of the innate immune program and are known to be expressed on immune cells as well as non-immune cells116 which includes a couple of vascular cell sorts like aortic ECs43, angiogenic ECs42, Sca-1+ vascular progenitor cells71, and VSMCs72, 73. PRRs can sense elements of exogenous microbes too as dangerous endogenous elements. These findings suggest a novel idea of conditional danger receptors that endogenous metabolites, when elevated to pathological concentrations, can trigger inflammation by binding to their intrinsic receptors as opposed to DAMPs/PAMPs for example TLRs or NLRs. This sort of intrinsic receptors for elevated endogenous metabolites are conditional danger receptors because they carry out physiological signaling function when metabolites are in physiological concentrations117, 118. The cellular “receptors, trouble-detectors and Akt3 drug metabolic sensors”79, which can recognize the risk components for atherogenesis119 for instance hyperlipidemia120 and hyperhomocysteinemia121, contribute considerably towards the innate immune functions of ECs. The roles of PRRs have already been characterized not too long ago as bridging innate immune sensory systems for exogenous infectious agents and endogenous metabolic DAMPs to initiation of inflammation51, 122, 123. As well as TLRs and NLRs, four extra DAMP receptor categories have beenArterioscler Thromb Vasc Biol. Author manuscript; accessible in PMC 2021 June 01.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptShao et al.Pagecharacterized124, 125: initial, transmembrane C-type lectin receptors (dendritic cell all-natural killer lectin group receptor 1 (DNGR1, receptor for F-actin), macrophage-inducible C-type lectin (MINCLE, receptor for spliceosome-associated protein 130 (SAP130), glycosylceramide), Dectin-1 (receptor for N-glycans) and Dectin-2116; second, retinoid acid inducible gene I (RIG-I, melanoma differentiation-associated protein 5 (MDA5) and RIGlike receptor dsRNA helicase (LGP2)116), third, cytosolic DNA sensors like AIM2 (absent in melanoma 2), cyclic GMP MP synthase (cGAS) and stimulator of Kainate Receptor custom synthesis interferon genes (STING)7.