Hergen Spits

..Here, we propose that ILCs should be categorized into three groups based on the cytokines that they can produce and the transcription factors that regulate their development and function...

..We also discuss the potential roles of ILCs in the pathology of immune-mediated inflammatory and infectious diseases including allergy...

..How ILC numbers are maintained is unknown. In this issue of Immunity, Qiu et al. (2012) report that the transcription factor aryl hydrocarbon receptor controls survival and function of gut-residing ILCs...

..Analogous to helper T cell subsets, these evolutionarily conserved yet distinct ILCs seem to have important roles in protective immunity, and their dysregulation can promote immune pathology...

..Tumanov et al. (Tumanov et al., 2011) demonstrate that crosstalk between ILCs and dendritic cells involving membrane-bound lymphotoxin in ILCs and its receptor is critical for protection against colitogenic bacteria...

..TSLP was capable of increasing the proportion and the absolute numbers of more mature human B cells. Overall, we provide evidence that TSLP supports human B-cell differentiation from fetal hematopoietic progenitors...

..Using this mouse model, the human immune system can be assessed for both fundamental and pre-clinical purposes...

..We propose a novel role for Spi-B in maintenance of germinal center and memory B cells by direct repression of major plasma cell factors and thereby plasma cell differentiation...

..Hence, we identify GATA3, potently regulated by TSLP, as an essential transcription factor for the function of human ILC2s...

..It is evident from our data that IFN-alpha inhibits the IL-7R signal transduction pathway, although this could not be attributed to interference with either IL-7R proximal (STAT5, Akt/PKB, Erk1/2) or distal (p27(kip1), pRb) events...

..These data indicate that DL1-induced activation of the Notch1 pathway controls the lineage commitment of early thymic precursors by altering the levels between Spi-B and GATA-3...

..Thus, up-regulation of BLIMP1 alone is not sufficient for differentiation of primary human B cells into plasma cells; concomitant down-regulation of BCL6 is absolutely required for completion of the plasma cell differentiation program...

..Inactivating p53 did not affect the development of CD34(+) cells into various mature leukocyte subsets, including T cells, but it conferred resistance to gamma-irradiation and other p53-dependent apoptotic stimuli to the T cells...

..However, in contrast to Spi-B, PU.1 knock down inhibited B cell and myeloid cell development as well. These results identify Spi-B as a key regulator of human pDC development...

..Upon activation, FoxP3+CD4+CD25+ Treg suppress potentially deleterious responses by autoreactive lymphocytes and maintain homeostasis within the developing fetus...

..Therapeutic applications may arise from these results because they provide a way to produce large numbers of autologous mature Ag-specific T cells in vitro from undifferentiated hemopoietic progenitors...

..Using Rag2(-/-)gamma(C)(-/-) mice on a Nude background, we demonstrated that development and induction of SHMs of human IgM(+)IgD(+)CD27(+) B cells can occur in a T cell-independent manner...

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..Fully human monoclonal antibodies directed against specific pathogens have a high therapeutic potential, but are difficult to generate...

..There was enrichment for CRTH2(+) ILCs in nasal polyps of chronic rhinosinusitis, a typical type 2 inflammatory disease. Our data identify a unique type of human ILC that provides an innate source of T helper type 2 (T(H)2) cytokines...

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..This method provides a new tool to study B cell biology and signal transduction through antigen-specific B cell receptors and for the rapid generation of high-affinity human monoclonal antibodies...

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..The frequency of the ILC1 subset was much higher in inflamed intestine of people with Crohn's disease, which indicated a role for these IFN-γ-producing ILC1 cells in the pathogenesis of gut mucosal inflammation...

..We describe here how to produce and monitor such "human immune system" (HIS) (BALB-Rag/gamma) mice, which offer large prospects for experimental study of the human immune system and as a preclinical screening tool...

..Superagonist anti-CD28 therapy could therefore be of clinical interest in humans, both for beneficial effect on thymic T-cell production as well as regulatory T-cell accumulation...

..The challenge of the near future will be to determine the role of pre-DC2 during thymic T cell development...

..This may require rejuvenation of the thymus. Alternatively, approaches to generate mature T cells independent of the thymus have gained considerable interest...

..Our results indicate that Spi-B is involved in the control of pDC development by limiting the capacity of progenitor cells to develop into other lymphoid lineages...

..These double- and triple-deficient mice all develop normal levels of CD4CD8 double negative and double positive thymocytes. These data indicate that PTEN is an important regulator of proliferation of developing T cells in the thymus...

..Here we review the current knowledge with regard to the transcription factors involved in the development and functions of ILCs...

..The use of regulatory gut-homing human CD4(+) cells may provide a novel approach to local delivery of immunomodulatory signals to the intestine in Crohn's disease...

..A paper in the current issue of the European Journal of Immunology indicates that the ligand-dependent transcription factor aryl hydrocarbon receptor is important for regulating IL-22 production of this new class of human Th cells...

..Our findings indicate that directed radiotherapy can improve the efficacy of tumor immunotherapy...

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..These data indicate that the thymus and the peripheral pDC2 develop independently of each other...

..Here, we discuss how ILCs can be categorized and summarize the current knowledge of Th1- and Th2-like ILCs with regard to the molecular mechanisms of development, effector functions, and their interplay with other cell types...

..This study sheds light over the relative contribution of ILC2s versus T helper type 2 cells (Th2) in type 2 mediated allergen-specific inflammation in the airways as discussed in this commentary...

..Here we discuss the potential and challenges of humanized mouse models for developing effective and affordable therapies and vaccines, which are desperately needed to combat these diseases...

..Taken together, these results show that ectopic hTERT expression not only protects proliferating T cells from replicative senescence but also confers resistance to apoptosis induced by oxidative stress...

..Data from experiments using reporter assays and overexpression of constitutively active IKK2 support the hypothesis that the STAT5 and nuclear factor-kappaB (NF-kappaB) pathways collaborate in HL genesis...