Yong Jun Liu

..Understanding IPC biology holds future promise for developing cures for infectious diseases, cancer, and autoimmune diseases...

..New reports now establish a direct link between TSLP expression and the pathogenesis of atopic dermatitis and asthma in vivo, and begin to reveal the molecular mechanisms underlying TSLP-induced allergic inflammation...

..We review recent progress on how TSLP expressed within thymus and peripheral lymphoid and nonlymphoid tissues regulates DC-mediated central tolerance, peripheral T cell homeostasis, and inflammatory Th2 responses...

..Therefore, TSLP and OX40 ligand may represent important targets for intervention of the initiation of allergic inflammatory responses...

..We conclude that OX40L on TSLP-activated DCs triggers Th2 cell polarization in the absence of IL-12, and propose that OX40L can switch IL-10-producing regulatory Th cell responses into TNF-alpha-producing inflammatory Th cell responses...

..This study reveals a novel function of GITR/GITRL in pDC-mediated coactivation of NK cells...

..These two novel functions of OX40L shed light on the mechanism by which OX40/OX40L regulates immunity and tolerance...

..The inability of TSLP to induce DC maturation without producing Th1- or Th2-polarizing cytokines may provide a thymic niche for T(R) development...

..The observation that a defect in DC apoptosis can independently lead to autoimmunity is consistent with a central role for these cells in maintaining immune self-tolerance...

..Our results provide a plausible explanation that IL-25 produced by innate effector eosinophils and basophils may augment the allergic inflammation by enhancing the maintenance and functions of adaptive Th2 memory cells...

..Thus, IL-25 is a critical factor regulating the initiation of innate and adaptive proallergic responses...

..Our findings demonstrate that mDC and pDCs are intrinsically different in the expression of costimulatory molecules that drive distinct types of T cell responses...

..These studies also challenge the paradigm that antibody responses are the primary of idiotype-specific antitumor effects and support the optimization of idiotype vaccines designed to induce primarily T-cell immunity...

..Stimulation of TLR7 or TLR9 leads to type I IFN responses through the MyD88 pathway. Thus, pDC/IPCs may play a central role in host defense against viral infection through the TLR7 and TLR9 system...

..Therefore, CD2AP positively regulates BDCA2/FcεR1γ signaling by forming a complex with SHIP1 to inhibit the E3 ubiquitin ligase Cbl...

..Knockdown of DHX9 expression in mDCs blocked the activation of NF-κB and IFN regulatory factor 3 by dsRNA. Collectively, these results suggest that DHX9 is an important RNA sensor that is dependent on IPS-1 to sense pathogenic RNA...

..5%. TSLP could only induce naive CD4(+) T cells to differentiate into Th2 cells in the presence of allogeneic mDCs. These results demonstrate that IL-7 and TSLP use different mechanisms to regulate human CD4(+) T cell homeostasis...

..We have therefore identified CD70 as an important factor in the regulation of B-cell growth and differentiation by pDCs...

..Therefore, the ILT7-Fc epsilonRI gamma receptor complex negatively regulates the innate immune functions of human pDCs...

..These results demonstrate for the first time that HDAC11 plays an essential role in regulating OX40L expression. Pharmacologic inhibition of HDAC11 may produce a favorable antitumor immune response in patients with HL...

..In addition, Treg selection requires the TCR signal and CD28 costimulation presented in cis on the same APC type in vivo. This study demonstrates a new role, to our knowledge, for HCs in the development of Tregs in thymus...

..Our results suggest that DDX41 is an additional DNA sensor that depends on STING to sense pathogenic DNA...

..The results point to potential therapeutic approaches to targeting the cellular and molecular mechanism underlying TSLP-mediated allergic inflammation...

..Our study demonstrates that PLSCR1 is a TLR9-interacting protein that plays an important role in pDC's type 1 IFN responses by regulating TLR9 trafficking to the endosomal compartment...

..We review recent progress on how TSLP expressed within thymus and peripheral lymphoid and nonlymphoid tissues regulates DC-mediated central tolerance, peripheral T cell homeostasis, and inflammatory Th2 responses...

..Therefore, by associating with Fc epsilon RI gamma, BDCA2 activates a novel BCR-like signaling pathway to regulate the immune functions of pDCs...

..The cross talk between mucosal epithelial cells and DC, mediated by HIV-induced TSLP, may be an important mechanism for the high rate of HIV infection in women through the vaginal mucosa...

..Our results demonstrate that pDC and mDC can interact synergistically to induce an Ag-specific antitumor immune response in vivo...

..Therefore, we propose that the functional plasticity of DCs relies on elaborate signal codes that are generated by different stimuli...

..In addition, these findings also provide an attainable explanation for the general paucity of antigen-triggered de novo generation of Foxp3(+) Tregs in the periphery...

..Thus, ICOS-L expression by melanoma tumor cells may directly drive Treg activation and expansion in the tumor microenvironment as another mechanism of immune evasion...

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..A critical question centers on how cytokines and lineage-restricted transcription factors operate molecularly to direct DC diversification. Here, we review recent findings that provide new insight into the DC developmental process...

..This novel mechanism of immune potentiation may be exploited for development of adjuvants for genetic vaccines against infectious pathogens and cancer...

..These observations suggest that MTA1-TG mice represent a new model of spontaneous DLBCL associated with high tumor incidence and could be used for therapeutic intervention studies...

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..This sensor was localized within the cytosol, independent of the endosomes. Thus, the DDX1-DDX21-DHX36 complex represents a dsRNA sensor that uses the TRIF pathway to activate type I IFN responses in the cytosol of mDCs...

..Our data establish a link between neutrophils, pDC activation, and autoimmunity in SLE, providing new potential targets for the treatment of this devastating disease...

..Our data thus demonstrated that activated pDCs are capable of initiating effective and systemic antitumor immunity through the orchestration of an immune cascade involving the sequential activation of NK cells, cDCs, and CD8(+) T cells...

..This review aims to describe the characterization of IL-23 and its receptor, its biological activities, as well as its involvement in the development of human Th17 cells and autoimmunity...

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..This study demonstrates that DHX9/DHX36 represent the MyD88-dependent DNA sensors in the cytosol of pDCs and suggests a much broader role for DHX helicases in viral sensing...

..Here, we review recent progress made on how TSLP expressed within the thymus and peripheral lymphoid and non-lymphoid tissues regulates DC-mediated T-cell development in the thymus and T-cell homeostasis in the periphery...

..These findings provide a mechanism for explaining how proteolytically active allergens could preferentially induce Th2 responses through limited maturation of DCs with reduced production of IL-12...

..IL-17-producing Treg cells may play critical roles in antimicrobial defense, while controlling autoimmunity and inflammation...

..The method was simple, efficient, and reproducible, and may have potential application for the development of adoptive immunotherapeutic strategies...

..Thus, our data uncover a fundamental role of an endogenous antimicrobial peptide in breaking innate tolerance to self-DNA and suggest that this pathway may drive autoimmunity in psoriasis...

..Several pDC receptors negatively regulate type I IFN responses by pDCs during viral infection and for normal homeostasis...

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..In this issue of the European Journal of Immunology, new insight is provided into how human pDC development is regulated by various transcription factors, in particular by the Ets family protein Spi-B and E-box protein E2-2...

..The recent research progress provides an in-depth understanding of the biology of pDCs and a sensible basis for future therapeutic interventions...

..Our results therefore show that GM-CSF controls the production of pDCs by employing STAT5 to suppress IRF8 and the pDC transcriptional network in lin- Flt3+ progenitors...

..These results, together with findings of TSLP expression in epithelial cells of mucosal lymphoid tissues and thymus, indicate that TSLP is involved in DC-mediated CD4(+) T cell homeostasis...

..pDCs derived from CMP express RAG gene products and show IgHD-J rearrangement, suggesting that pDC represent a unique lineage whose gene expression program shows substantial plasticity...

..Consistently, STAT3 stimulates Flt3L-responsive expression of the pDC regulator Tcf4 (E2-2). These data suggest that STATs contribute to DC development by controlling transcription factors involved in lineage differentiation...

..Inflammatory cells, particularly mast cells, have been shown to play key roles in some cancers. We carried out this study to test the hypothesis that mast cells in the tumor microenvironment are essential for PDAC tumorigenesis...

..Readily induced by IFN and other proinflammatory cytokines, BST2 may modulate the human pDC's IFN responses through ILT7 in a negative feedback fashion...

..This study provides formal proof that the plasticity of DC subsets is limited and that different DC subsets evolve to perform distinct functions in linking innate and adaptive immunity...

..Plasmacytoid dendritic cells (pDCs) have potential influence on innate and adaptive immune responses. In this issue of Immunity, Takagi et al. (2011) established mice lacking pDCs and explored the impact of pDC ablation in vivo...

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..This suggests that DcR3.Fc may act not only as a decoy receptor to FasL and LIGHT, but also as an effector molecule to skew T cell response to the Th2 phenotype...

..Thus, epithelial- and stromal-cell-derived TSLP might represent one of the factors initiating the allergic responses, and could be a target for a curative therapeutic approach to allergy...

..This culture system, combined with the use of adult peripheral blood CD34+ HPCs purified from G-CSF-mobilized donors, permits the generation of more than 10(9) IPCs from a single blood donor...

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..Our results demonstrate the highly heterogeneous nature of hepatic DC, which is in agreement with the unique requirements for APC in the complex liver environment...

..Thus, the net effect of antigen dose, the state of maturation of the DCs together with the stimulation of DCs by pathogen-derived products, will determine whether a Th1 or Th2 response develops...

..DC2 can be used as tool to drive potent antigen specific Tr-cell differentiation and expansion in vitro and in vivo...

..Therefore, we must study the dynamics of the DC network in response to microbial invasion. Despite the difficulty of comparing the DC systems of humans and mice, recent work has revealed much common ground...

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..Human IPCs and mouse IPCs display different ability to produce IL-12p70. Large numbers of mouse IPCs can now be obtained from total bone marrow culture...

..TSLP expression was associated with Langerhans cell migration and activation in situ. These findings shed new light on the function of human TSLP and the role played by epithelial cells and DCs in initiating allergic inflammation...

..This study demonstrates that TLR9 stimulation can promote PDC-mediated generation of CD4(+)CD25(+) Treg cells and suggests PDCs may play an important role in the maintenance of immunological tolerance...

..Here we review recent progress on the characterization of plasmacytoid dendritic cell origin, development, migration and function in immunity and tolerance, as well as their effect on human diseases...

..The development of different populations of DCs is differentially regulated by various transcription factors and cytokines. This review summarizes the recent advances made in the field of DC development...

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..These findings uncover a novel innate immune pathway for triggering a common human autoimmune disease and suggest that PDCs and PDC-derived IFN-alpha represent potential early targets for the treatment of psoriasis...

..Thus, TLR-induced differentiation of monocytes into either macrophages or dendritic cells seems to crucially influence effective host defenses in human infectious disease...

..TSLP is present at high levels in the epidermis of atopic dermatitis where it appears to trigger emigration of epidermal Langerhans cells (LCs); however, nothing else is known about the influence of TSLP on LCs...

..Moreover, TSLP increases the sensitivity of human CD4(+) T cells to low doses of IL-2, augmenting responsiveness of these cells to TCR engagement. Our results establish that human CD4(+) T cells are direct targets for TSLP...

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..Thus, TSLP is a major regulatory cytokine for IL-12 production by DCs, and TSLP-activated DCs could promote the persistence of Th2 inflammation even in the presence of IL-12-inducing signals...

..These findings suggest that BCG might be a useful adjuvant for the treatment of allergic diseases that are triggered by TSLP...

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..The comparative study indicates that UC is an excellent alternative to BM as a source of MSC for cell therapies...

..Such tumor antigen-specific T regs were not detected in healthy individuals. These tumor antigen-specific T regs might thus represent another target for immunotherapy of metastatic melanoma...

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..Thus, the balance between IPCs and HIV replication might be critical in determining the control or progression of HIV infection...

..Our results pinpoint a new role of pDCs in the induction of antiviral T-cell responses and suggest that these DCs play a prominent role in the adaptive immune response against viruses...

..Elucidating the cellular and molecular mechanisms that modulate the functions of the 2 DC subsets will lead to an understanding of the pathogenesis of various immune-related diseases and to the development of novel immunologic therapies...

..Finally, the implications of the recent advances in the understanding of molecular genetic mechanisms of body weight regulation on prevention and therapeutic intervention of obesity will be discussed...

..This HIV-1-induced maturation of both DC subsets may explain their disappearance from the blood of patients with high viral loads and may have important consequences on HIV-1 cellular transmission and HIV-1-specific T-cell responses...

..Therefore, it would be possible to use stromal cells expressing HAPO gene as seed cells in the bone marrow transplantation...

..To identify the molecular regulation of TSLP receptor (TSLPR) and IL-7Ralpha co-expression; 3. To elicidate the molecular mechanisms by which TSLP-activated DCs induce TH2 differentiation. ..

..The proposed studies will provide insight into the pathogenic mechanisms of allergic inflammation and define novel targets for developing innovative therapies for allergic asthma and atopy. ..

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