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  • Clinton Wilhelmsen posted an update 6 years, 4 months ago

    The myeloid DCs, presently termed standard DCs (cDCs), are further subdivided into many subsets present in immune and nonimmune tissues and organs specialized to carry out various functions as get Elesclomol described beneath. CD11c has been applied as a common marker of murine cDCs even though additional markers have already been employed to distinguish these cells from other leukocytes for instance NK cells and B cells that can also express it. Indeed, all cDC populations (except pre-DCs) are characterized by expressing higher levels of CD11c [11, 12]. In the steady state cDCs present in lymphoid organs and tissues originated from bone marrow precursors. As extensively reviewed by Liu and Nussenzweig, 2010 [11], the mouse bone marrow harbors a common DC precursor (CDP) characterized by high expression of CD115 and Flt3, low expression of CD117 (CD117lo ), and is damaging for lineage markers CD3, NK1.1, B220, TER-119, and Gr-1 (Lin- ) [13]. This precursor is derived from a frequent monocyte and DC precursor also present in the bone marrow [11, 13]. The CDP gives rise to a pre-DC circulating precursor (CD11c+ MHCII- SIRPlo ) that quickly reaches the lymphoidJournal of Biomedicine and BiotechnologyLymph node (resident) CD11chi MHCII+ CD8+ CD205+ CD11chi MHCII+ CD8- CD11b+ (migratory) CD11c+ MHCIIhi langerin+ CD40hiSpleen CD11chi MHCII+ CD8+ CD205+ SIRP- CD11b- CD11chi MHCII+ CD8- 33D1+ SIRP+ CD11b+Lung, liver, kidney CD11chi MHC+ CD103+ CD11b- CD11chi MHC+ CD103- CD11bhiThymus CD8+ CD205+ CD11blo CD8- SIRP+ CD11bhiIntestine CD11chi MHC+ CD103+ CD11blo CX3CR1- (PP) CD11chi MHC+ CD103- CD11bhi CX3CR1+ (LP) CD11chi MHC+ CD103+ CD11b+ CX3CR1- (LP)Circulation 02699931.2015.1049516 CD11c+ MHCII- SIRPlo (Pre-DCs) Bone marrow Lin- CD115+ Flt3+ CD117lo (CDP)Langerhams cells (dermis) CD103+ CD11blo langerin+ CD103- CD11bhi langerin- (epidermis) CD11chi CD205lo langerin+ EpCAMhiFigure 1: Standard murine DCs inside the steady state. Numerous DC subpopulations have already been described inside the mouse model colonizing lymphoid organs and also other tissues. Figure adapted from Motifolio Biomedical Toolkit Suite.GM-CSF and/or IL-4 generates high amounts of dendritic cells, capable of stimulating T cells in vitro and in vivo, which have been extensively employed so as to investigate DC: T cell interactions, identify the efficacy of DC-based vaccines, and determine their role in pathological conditions such infectious ailments or tumor models [27?4]. Alternatively, in vitro generated DCs is usually obtained from bone marrow progenitors by therapy with fms-related tyrosine kinase three ligand (Flt3) and cytokines such as IL-6, stem cell factor, IL3, or insulin-like development aspect [25, 26, 35]. The DC populations generated upon culture of those precursors with Flt3 happen to be regarded to far more closely resemble CD8+ splenic DCs, especially in their capability of producing IL12 and or cross-present antigens, even though lacking expression of CD8 [36]. Ultimately, Flt3 may be also utilized for expansion of murine DCs in vivo [35, 37].four. Murine DC Subsets in the course of Inflammation and DiseaseIt has been postulated that within the steady state murine DCs only originate from DC precursors, although pnas.1408988111 through inflammatory or pathological settings they may also arise frommonocytes and colonize lymphoid organs or nonimmune tissues [38?2]. In addition, it has also been demonstrated that, upon CD11c depletion, monocytes can contribute to DC repopulation in the degree of the intestine [43].