Mus musculus
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PROVIDER: PRJNA153017 | ENA |
REPOSITORIES: ENA
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Project description:The phenotypic and functional dichotomy between IRF8+ type 1 and IRF4+ type 2 conventional dendritic cells (cDC1-cDC2) is well accepted; it is unknown how robust this dichotomy is under inflammatory conditions, when additionally monocyte-derived cells (MCs) become competent antigen presenting cells (APC). Using single-cell technologies in models of respiratory viral infection, we found that lung cDC2s acquired expression of Fc receptor CD64 shared with MCs, and of IRF8 shared with cDC1s. These inflammatory (Inf-)cDC2s were superior in inducing CD4+ T helper (Th) cell polarization while simultaneously presenting antigen to CD8+ T cells. When carefully separated from inf-cDC2s, MCs lacked APC function. Inf-cDC2 matured in response to cell-intrinsic toll-like receptor and type 1 interferon receptor signaling, upregulated an IRF8-dependent maturation module and acquired antigens via convalescent serum and Fc receptors. Since hybrid inf-cDC2s are easily confused with monocyte-derived cells, their existence could explain why APC functions have been attributed to MCs.
2020-05-08 | GSE149618 | GEO
Project description:The phenotypic and functional dichotomy between IRF8+ type 1 and IRF4+ type 2 conventional dendritic cells (cDC1-cDC2) is well accepted; it is unknown how robust this dichotomy is under inflammatory conditions, when additionally monocyte-derived cells (MCs) become competent antigen presenting cells (APC). Using single-cell technologies in models of respiratory viral infection, we found that lung cDC2s acquired expression of Fc receptor CD64 shared with MCs, and of IRF8 shared with cDC1s. These inflammatory (Inf-)cDC2s were superior in inducing CD4+ T helper (Th) cell polarization while simultaneously presenting antigen to CD8+ T cells. When carefully separated from inf-cDC2s, MCs lacked APC function. Inf-cDC2 matured in response to cell-intrinsic toll-like receptor and type 1 interferon receptor signaling, upregulated an IRF8-dependent maturation module and acquired antigens via convalescent serum and Fc receptors. Since hybrid inf-cDC2s are easily confused with monocyte-derived cells, their existence could explain why APC functions have been attributed to MCs.
2020-05-08 | GSE149617 | GEO
Project description:In lupus autoimmunity, pathogenic IgG autoantibodies that fix complement and bind FcGammaR on inflammatory cells, are produced with help from T helper (Th1 and Th17) cells specific for peptides from nucleosomes of apoptotic cells; and these Th cells also infiltrate vital organs (1-9). Macrophages (e.g. tingible body MΦ), and DCs are normally tolerant to apoptotic cell antigens (10), but they are activated to present such autoantigens after binding to IgG immune complexes (IC) containing apoptotic cell derived DNA/RNA, which then dually stimulate their TLR and FcGammaR (11-16). Hence, to generate the activating IC, IgG-switched autoantibodies have to be made first by T cell help. Moreover, B cells become efficient antigen presenting cells (APC) to Th cells pre-primed by other APC (17), or if the B cells have developed high affinity somatically mutated receptors by T cell help (18). Thus, conventional APCs participate as disease progresses, but it is unknown who initially primes autoimmune Th cells. We fractionated spleen cells of lupus prone SNF1 mice in search of such APC. To produce lupus-prone SNF1 mice, NZB and SWR mice were purchased from The Jackson Laboratory, ME to breed the lupus-prone SNF1 hybrids (19). Female SNF1 mice, like BWF1, have high serum levels of IgG class anti-DNA and other anti-nuclear autoantibodies by 2 mo, and spontaneously begin to develop severe lupus nephritis by 5 mo age (20). We depleted spleen cells of lupus-prone SNF1 mice of cells with mature lineage markers, including conventional APC, and then isolated pure CD117+ (c-Kit+ or K+) cells from the lineage– (Lin– or L–) cells. These Lin–c-Kit+pure cells, which had morphology of hematopoietic progenitor cells, were the main type of APC inducing nuclear autoantigen-specific T helper cell (Th17) response upon feeding them with nucleosomes. These Lin–c-Kit+pure cell isolate is called "LinminuscKitplus pure" in the Sample titles shown below. CD117 (c-Kit) is also a marker for macrophage/dendritic cell precursors (MDP), which also express CX3CR1 (21-23). Therefore, from T and B-cell depleted spleen cells, we sorted out CD117+CX3CR1–, CD117+CX3CR1+, CD117–CX3CR1+, and CD117–CX3CR1– cell subsets, and then tested their abilities to induce Th responses to nucleosomes. The CD117+CX3CR1– cells were Lin– (Lin–c-Kit+CX3CR1– or L–K+Cx–; named as "LinminuscKitplusCX3CR1minus" in the sample titles below) were very similar to L–K+pure cells (LinminuscKitplus pure), which are also CX3CR1–, although isolated in a different way. Therefore, we compared gene expression profiles of nucleosome-pulsed APC that were isolated in those two ways, namely purified Lin–c-Kit+ pure (LinminuscKitplus pure) cells or the Lin–c-Kit+CX3CR1– (LinminuscKitplusCX3CR1minus) cell subset, with other types of APCs, namely the Lin–c-Kit+CX3CR1+ subset (named as "LinminuscKitminusCX3CR1plus" in sample titles below), or CD11c+CD11blowc-Kit– cells (Dendritic cells in the sample titles below). REFERENCES 1. Adams, S., P. Leblanc, and S. K. Datta. 1991. Junctional region sequences of T-cell receptor b chain genes expressed by pathogenic anti-DNA autoantibody-inducing T helper cells from lupus mice: Possible selection by cationic autoantigens. Proc. Natl. Acad. Sci. USA. 88:11271-11275. 2. Mohan, C., S. Adams, V. Stanik, and S. K. Datta. 1993. Nucleosome: A major immunogen for the pathogenic autoantibody-inducing T cells of lupus. J. Exp. Med. 177:1367-1381. 3. Kaliyaperumal, A., C. Mohan, W. Wu, and S. K. Datta. 1996. Nucleosomal peptide epitopes for nephritis-inducing T helper cells of murine lupus. J. Exp. Med. 183:2459-2469. 4. Lu, L., A. Kaliyaperumal, D. T. Boumpas, and S. K. Datta. 1999. Major peptide autoepitopes for nucleosome-specific T cells of human lupus. J. Clin. Invest. 104:345-355. 5. Balomenos, D., R. Rumold, and A. N. Theofilopoulos. 1998. Interferon-gamma is required for lupus-like disease and lymphoaccumulation in MRL-lpr mice. J. Clin. Invest. 101:364-371. 6. Doreau, A., A. Belot, J. Bastid, B. Riche, M. C. Trescol-Biemont, B. Ranchin, N. Fabien, P. Cochat, C. Pouteil-Noble, P. Trolliet, I. Durieu, J. Tebib, B. Kassai, S. Ansieau, A. Puisieux, J. F. Eliaou, and N. Bonnefoy-Berard. 2009. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat. Immunol. 10:778-785. 7. Kang, H.-K., M. Liu, and S. K. Datta. 2007. Low-Dose Peptide Tolerance Therapy of Lupus Generates Plasmacytoid Dendritic Cells That Cause Expansion of Autoantigen-Specific Regulatory T Cells and Contraction of Inflammatory Th17 Cells (cover page Figure). J Immunol 178:7849-7858. 8. Hsu, H. C., P. Yang, J. Wang, Q. Wu, R. Myers, J. Chen, J. Yi, T. Guentert, A. Tousson, A. L. Stanus, T. V. Le, R. G. Lorenz, H. Xu, J. K. Kolls, R. H. Carter, D. D. Chaplin, R. W. Williams, and J. D. Mountz. 2008. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat. Immunol. 9:166-175. 9. Crispin, J. C., M. Oukka, G. Bayliss, R. A. Cohen, C. A. Van Beek, I. E. Stillman, V. C. Kyttaris, Y. T. Juang, and G. C. Tsokos. 2008. Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. J. Immunol. 181:8761-8766. 10. Steinman, R. M., D. Hawiger, and M. C. Nussenzweig. 2003. Tolerogenic dendritic cells. Annu Rev Immunol 21:685-711. 11. Leadbetter, E. A., I. R. Rifkin, A. M. Hohlbaum, B. C. Beaudette, M. J. Shlomchik, and A. Marshak-Rothstein. 2002. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature 416:595-598. 12. Blanco, P., A. K. Palucka, M. Gill, V. Pascual, and J. Banchereau. 2001. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science 294:1540-1543. 13. Means, T. K., E. Latz, F. Hayashi, M. R. Murali, D. T. Golenbock, and A. D. Luster. 2005. Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J. Clin. Invest. 115:407-417. 14. Bave, U., M. Magnusson, M. L. Eloranta, A. Perers, G. V. Alm, and L. Ronnblom. 2003. Fc gamma RIIa is expressed on natural IFN-alpha-producing cells (plasmacytoid dendritic cells) and is required for the IFN-alpha production induced by apoptotic cells combined with lupus IgG. J Immunol 171:3296-3302. 15. Niewold, T. B., J. A. Kelly, M. H. Flesch, L. R. Espinoza, J. B. Harley, and M. K. Crow. 2008. Association of the IRF5 risk haplotype with high serum interferon-alpha activity in systemic lupus erythematosus patients. Arthritis Rheum. 58:2481-2487. 16. Teichmann, L. L., M. L. Ols, M. Kashgarian, B. Reizis, D. H. Kaplan, and M. J. Shlomchik. 2010. Dendritic cells in lupus are not required for activation of T and B cells but promote their expansion, resulting in tissue damage. Immunity 33:967-978. 17. Rock, K. L., B. Benacerraf, and A. K. Abbas. 1984. Antigen presentation by hapten-specific B lymphocytes. J. Exp. Med. 160:1102-1113. 18. Chaturvedi, A., D. Dorward, and S. K. Pierce. 2008. The B cell receptor governs the subcellular location of Toll-like receptor 9 leading to hyperresponses to DNA-containing antigens. Immunity 28:799-809. 19. Datta, S. K., and R. S. Schwartz. 1976. Genetics of expression of xenotropic virus and autoimmunity in NZB mice. Nature. 263:412-415. 20. Datta, S. K., N. Manny, C. Andrzejewski, J. Andre-Schwartz, and R. S. Schwartz. 1978. Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand Black mice. I. xenotropic virus. J. Exp. Med. 147:854-871. 21. Fogg, D. K., C. Sibon, C. Miled, S. Jung, P. Aucouturier, D. R. Littman, A. Cumano, and F. Geissmann. 2006. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 311:83-87. 22. Onai, N., A. Obata-Onai, M. A. Schmid, T. Ohteki, D. Jarrossay, and M. G. Manz. 2007. Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nat. Immunol. 8:1207-1216. 23. Waskow, C., K. Liu, G. Darrasse-Jeze, P. Guermonprez, F. Ginhoux, M. Merad, T. Shengelia, K. Yao, and M. Nussenzweig. 2008. The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nat. Immunol. 9:676-683. 24. Du, P., W. A. Kibbe, and S. M. Lin. 2008. lumi: a pipeline for processing Illumina microarray. Bioinformatics 24:1547-1548. 25. Lin, S. M., P. Du, W. Huber, and W. A. Kibbe. 2008. Model-based variance-stabilizing transformation for Illumina microarray data. Nucleic Acids Res 36:e11. 26. Du, P., W. A. Kibbe, and S. M. Lin. 2007. nuID: a universal naming scheme of oligonucleotides for illumina, affymetrix, and other microarrays. Biol Direct 2:16. 27. Wettenhall, J. M., and G. K. Smyth. 2004. limmaGUI: a graphical user interface for linear modeling of microarray data. Bioinformatics 20:3705-3706. Gene profiling microarray and data analysis. Spleen cells from 3 batches of three 5 mo SNF1 female mice each time were used to obtain three independent isolations of each type of APC population. Total RNA was purified from each APC after incubation with nucleosomes (20µg/ml) for 6h. RNA expression analysis of each type of APC isolate in triplicate was performed at our Genomics Core Facility using Illumina Mouse WG-6 v2.0 Expression Beadchips, which provides coverage of around 45,281 genes and expressed sequence tags. Raw signal intensities of each probe were obtained using data analysis software (Beadstudio; Illumina) and imported to the Lumi package of Bioconductor for data analysis. Before transformation and normalization (24-26), A/P call detection was performed based on detection p value. 20,890 out of 45,281 probes with less than 0.01 were considered as valid signals. For each pairs of four comparisons: Lin–c-Kit+CX3CR1– versus Lin–c-Kit+ CX3CR1+; Lin–c-Kit+pure vs. Lin–c-Kit+CX3CR1+; Lin–c-Kit+CX3CR1– vs. DC; and Lin–c-Kit+pure vs. DC; differentially expressed genes were identified using an Analysis of Variance (ANOVA) model with empirical Bayesian variance estimation (27). Thus, 1,619 genes were identified as being differentially expressed (up or down) on the basis of a statistically significant (raw P-value < 0.01 and false discovery rate adjusted P-value < 0.05), and 1.5-fold change (up or down) in expression level in at least one of the comparisons, and out of these 230 genes were significantly UP-regulated by the above criteria in all 4 pair comparisons.
2012-06-20 | E-GEOD-36284 | biostudies-arrayexpress
Project description:Analysis of lung CD11c+ antigen presenting cells (APCs) isolated from wildtype or Mir22-/- mice exposed to nanoparticulate carbon black (nCB) for one month. MiR-22 plays important roles in nCB induced experimental emphysema through regulating APC activation. Results provide insight into the biological role and target genes of miR-22. Smoking-related emphysema is a chronic inflammatory disease driven by T helper 17 (TH17) cells through molecular mechanisms that remain obscure. Here we have explored the role of microRNA-22 (miR-22) in emphysema. MiR-22 was upregulated in lung myeloid dendritic cells (mDCs) of smokers with emphysema and antigen-presenting cells (APCs) of mice exposed to smoke or nanoparticulate carbon black (nCB) through a mechanism involving NF-kappaB. MiR-22-deficient mice, but not wild-type, showed attenuated TH17 responses and failed to develop emphysema after exposure to either smoke or nCB. We further show that miR-22 controls APC activation and TH17 responses through activation of AP-1 transcription factor complexes and histone deacetylase (HDAC) 4. Thus, miR-22 is a critical regulator of both emphysema and TH17 responses. Lung APCs were isolated from PBS (reference groups) or nCB exposed wildtype or Mir22-/- mice, total four groups. There were three replicates in each group.
2015-09-05 | E-GEOD-72734 | biostudies-arrayexpress
Project description:Transcriptional profiles of four different myeloid antigen presenting cell (APC) subsets (BDCA-1+ circulating myeloid dendritic cells, CD14+ monocytes, and in vitro generated immature and mature monocyte-derived dendritic cells) were used for comprehensive transcriptome analysis. Based on the gene expression profiling data, a quantitative relationship between myeloid APC in functionally related gene spaces was established. Keywords = myeloid antigen presenting cells Keywords = dendritic cell subsets Keywords: repeat sample
2017-12-21 | GSE2215 | GEO
Project description:In lupus autoimmunity, pathogenic IgG autoantibodies that fix complement and bind FcGammaR on inflammatory cells, are produced with help from T helper (Th1 and Th17) cells specific for peptides from nucleosomes of apoptotic cells; and these Th cells also infiltrate vital organs (1-9). Macrophages (e.g. tingible body MΦ), and DCs are normally tolerant to apoptotic cell antigens (10), but they are activated to present such autoantigens after binding to IgG immune complexes (IC) containing apoptotic cell derived DNA/RNA, which then dually stimulate their TLR and FcGammaR (11-16). Hence, to generate the activating IC, IgG-switched autoantibodies have to be made first by T cell help. Moreover, B cells become efficient antigen presenting cells (APC) to Th cells pre-primed by other APC (17), or if the B cells have developed high affinity somatically mutated receptors by T cell help (18). Thus, conventional APCs participate as disease progresses, but it is unknown who initially primes autoimmune Th cells. We fractionated spleen cells of lupus prone SNF1 mice in search of such APC. To produce lupus-prone SNF1 mice, NZB and SWR mice were purchased from The Jackson Laboratory, ME to breed the lupus-prone SNF1 hybrids (19). Female SNF1 mice, like BWF1, have high serum levels of IgG class anti-DNA and other anti-nuclear autoantibodies by 2 mo, and spontaneously begin to develop severe lupus nephritis by 5 mo age (20). We depleted spleen cells of lupus-prone SNF1 mice of cells with mature lineage markers, including conventional APC, and then isolated pure CD117+ (c-Kit+ or K+) cells from the lineage– (Lin– or L–) cells. These Lin–c-Kit+pure cells, which had morphology of hematopoietic progenitor cells, were the main type of APC inducing nuclear autoantigen-specific T helper cell (Th17) response upon feeding them with nucleosomes. These Lin–c-Kit+pure cell isolate is called "LinminuscKitplus pure" in the Sample titles shown below. CD117 (c-Kit) is also a marker for macrophage/dendritic cell precursors (MDP), which also express CX3CR1 (21-23). Therefore, from T and B-cell depleted spleen cells, we sorted out CD117+CX3CR1–, CD117+CX3CR1+, CD117–CX3CR1+, and CD117–CX3CR1– cell subsets, and then tested their abilities to induce Th responses to nucleosomes. The CD117+CX3CR1– cells were Lin– (Lin–c-Kit+CX3CR1– or L–K+Cx–; named as "LinminuscKitplusCX3CR1minus" in the sample titles below) were very similar to L–K+pure cells (LinminuscKitplus pure), which are also CX3CR1–, although isolated in a different way. Therefore, we compared gene expression profiles of nucleosome-pulsed APC that were isolated in those two ways, namely purified Lin–c-Kit+ pure (LinminuscKitplus pure) cells or the Lin–c-Kit+CX3CR1– (LinminuscKitplusCX3CR1minus) cell subset, with other types of APCs, namely the Lin–c-Kit+CX3CR1+ subset (named as "LinminuscKitminusCX3CR1plus" in sample titles below), or CD11c+CD11blowc-Kit– cells (Dendritic cells in the sample titles below). REFERENCES 1. Adams, S., P. Leblanc, and S. K. Datta. 1991. Junctional region sequences of T-cell receptor b chain genes expressed by pathogenic anti-DNA autoantibody-inducing T helper cells from lupus mice: Possible selection by cationic autoantigens. Proc. Natl. Acad. Sci. USA. 88:11271-11275. 2. Mohan, C., S. Adams, V. Stanik, and S. K. Datta. 1993. Nucleosome: A major immunogen for the pathogenic autoantibody-inducing T cells of lupus. J. Exp. Med. 177:1367-1381. 3. Kaliyaperumal, A., C. Mohan, W. Wu, and S. K. Datta. 1996. Nucleosomal peptide epitopes for nephritis-inducing T helper cells of murine lupus. J. Exp. Med. 183:2459-2469. 4. Lu, L., A. Kaliyaperumal, D. T. Boumpas, and S. K. Datta. 1999. Major peptide autoepitopes for nucleosome-specific T cells of human lupus. J. Clin. Invest. 104:345-355. 5. Balomenos, D., R. Rumold, and A. N. Theofilopoulos. 1998. Interferon-gamma is required for lupus-like disease and lymphoaccumulation in MRL-lpr mice. J. Clin. Invest. 101:364-371. 6. Doreau, A., A. Belot, J. Bastid, B. Riche, M. C. Trescol-Biemont, B. Ranchin, N. Fabien, P. Cochat, C. Pouteil-Noble, P. Trolliet, I. Durieu, J. Tebib, B. Kassai, S. Ansieau, A. Puisieux, J. F. Eliaou, and N. Bonnefoy-Berard. 2009. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat. Immunol. 10:778-785. 7. Kang, H.-K., M. Liu, and S. K. Datta. 2007. Low-Dose Peptide Tolerance Therapy of Lupus Generates Plasmacytoid Dendritic Cells That Cause Expansion of Autoantigen-Specific Regulatory T Cells and Contraction of Inflammatory Th17 Cells (cover page Figure). J Immunol 178:7849-7858. 8. Hsu, H. C., P. Yang, J. Wang, Q. Wu, R. Myers, J. Chen, J. Yi, T. Guentert, A. Tousson, A. L. Stanus, T. V. Le, R. G. Lorenz, H. Xu, J. K. Kolls, R. H. Carter, D. D. Chaplin, R. W. Williams, and J. D. Mountz. 2008. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat. Immunol. 9:166-175. 9. Crispin, J. C., M. Oukka, G. Bayliss, R. A. Cohen, C. A. Van Beek, I. E. Stillman, V. C. Kyttaris, Y. T. Juang, and G. C. Tsokos. 2008. Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. J. Immunol. 181:8761-8766. 10. Steinman, R. M., D. Hawiger, and M. C. Nussenzweig. 2003. Tolerogenic dendritic cells. Annu Rev Immunol 21:685-711. 11. Leadbetter, E. A., I. R. Rifkin, A. M. Hohlbaum, B. C. Beaudette, M. J. Shlomchik, and A. Marshak-Rothstein. 2002. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature 416:595-598. 12. Blanco, P., A. K. Palucka, M. Gill, V. Pascual, and J. Banchereau. 2001. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science 294:1540-1543. 13. Means, T. K., E. Latz, F. Hayashi, M. R. Murali, D. T. Golenbock, and A. D. Luster. 2005. Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J. Clin. Invest. 115:407-417. 14. Bave, U., M. Magnusson, M. L. Eloranta, A. Perers, G. V. Alm, and L. Ronnblom. 2003. Fc gamma RIIa is expressed on natural IFN-alpha-producing cells (plasmacytoid dendritic cells) and is required for the IFN-alpha production induced by apoptotic cells combined with lupus IgG. J Immunol 171:3296-3302. 15. Niewold, T. B., J. A. Kelly, M. H. Flesch, L. R. Espinoza, J. B. Harley, and M. K. Crow. 2008. Association of the IRF5 risk haplotype with high serum interferon-alpha activity in systemic lupus erythematosus patients. Arthritis Rheum. 58:2481-2487. 16. Teichmann, L. L., M. L. Ols, M. Kashgarian, B. Reizis, D. H. Kaplan, and M. J. Shlomchik. 2010. Dendritic cells in lupus are not required for activation of T and B cells but promote their expansion, resulting in tissue damage. Immunity 33:967-978. 17. Rock, K. L., B. Benacerraf, and A. K. Abbas. 1984. Antigen presentation by hapten-specific B lymphocytes. J. Exp. Med. 160:1102-1113. 18. Chaturvedi, A., D. Dorward, and S. K. Pierce. 2008. The B cell receptor governs the subcellular location of Toll-like receptor 9 leading to hyperresponses to DNA-containing antigens. Immunity 28:799-809. 19. Datta, S. K., and R. S. Schwartz. 1976. Genetics of expression of xenotropic virus and autoimmunity in NZB mice. Nature. 263:412-415. 20. Datta, S. K., N. Manny, C. Andrzejewski, J. Andre-Schwartz, and R. S. Schwartz. 1978. Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand Black mice. I. xenotropic virus. J. Exp. Med. 147:854-871. 21. Fogg, D. K., C. Sibon, C. Miled, S. Jung, P. Aucouturier, D. R. Littman, A. Cumano, and F. Geissmann. 2006. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 311:83-87. 22. Onai, N., A. Obata-Onai, M. A. Schmid, T. Ohteki, D. Jarrossay, and M. G. Manz. 2007. Identification of clonogenic co
2012-06-21 | GSE36284 | GEO
Project description:Live attenuated vaccines are often superior to dead vaccines, yet the immunological mechanisms remain largely obscure. We have recently uncovered an inherent capacity of antigen-presenting cells (APC) to discriminate live from killed bacteria by virtue of vita-PAMPs. Here we found that innate recognition of bacterial viability strongly promotes the differentiation of fully functional T follicular helper (TFH) cells. We identify TLR8 and its signaling adaptor MyD88 as critical sensor for bacterial viability in human APC, activation of which is required and sufficient to induce selective transcriptional remodeling and the production of TFH promoting signals like IL-12. Activators of other TLRs including licensed vaccine adjuvants fail to do so. Consequently, vita-PAMP receptors such as TLR8 represent promising targets for adjuvants to improve the efficacy of modern inanimate subunit vaccines. Human monocytes were infected with live or heat-killed E. coli for 6h.
2016-04-06 | E-GEOD-68255 | biostudies-arrayexpress
Project description:Analysis of lung CD11c+ antigen presenting cells (APCs) isolated from wildtype or Mir22-/- mice exposed to nanoparticulate carbon black (nCB) for one month. MiR-22 plays important roles in nCB induced experimental emphysema through regulating APC activation. Results provide insight into the biological role and target genes of miR-22. Smoking-related emphysema is a chronic inflammatory disease driven by T helper 17 (TH17) cells through molecular mechanisms that remain obscure. Here we have explored the role of microRNA-22 (miR-22) in emphysema. MiR-22 was upregulated in lung myeloid dendritic cells (mDCs) of smokers with emphysema and antigen-presenting cells (APCs) of mice exposed to smoke or nanoparticulate carbon black (nCB) through a mechanism involving NF-kappaB. MiR-22-deficient mice, but not wild-type, showed attenuated TH17 responses and failed to develop emphysema after exposure to either smoke or nCB. We further show that miR-22 controls APC activation and TH17 responses through activation of AP-1 transcription factor complexes and histone deacetylase (HDAC) 4. Thus, miR-22 is a critical regulator of both emphysema and TH17 responses.
2015-09-05 | GSE72734 | GEO
Project description:Given the importance of sustained antigen presentation in maintenance of lymph node (LN) immune responses, we hypothesized that vaccine antigen availability and antigen-presenting cell (APC) populations may affect LN expansion. Compared to LNs of mice given the full MPS vaccine, LNs of mice given an MPS vaccine without antigen became prominently less enlarged and contracted sooner.To identify potential mediators of this differential, antigen-dependent response, we next focused the analysis of our scRNA-seq dataset on LN APC populations.
2024-04-05 | E-MTAB-13698 | biostudies-arrayexpress