Importance of EMT Factor ZEB1 in cDC1 'MutuDC Line' Mediated Induction of Th1 Immune Response
| Autor: | Shuchi Smita, Abdul Ahad, Arup Ghosh, Viplov K. Biswas, Marianna M. Koga, Bhawna Gupta, Hans Acha-Orbea, Sunil K. Raghav |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine Adoptive cell transfer Adaptive Immunity CD8-Positive T-Lymphocytes Lymphocyte Activation Mice 0302 clinical medicine Adaptive Immunity/immunology Adoptive Transfer/methods Animals CD4-Positive T-Lymphocytes/immunology CD8-Positive T-Lymphocytes/immunology Cell Differentiation/immunology Cells Cultured Coculture Techniques/methods Dendritic Cells/immunology Epithelial-Mesenchymal Transition/immunology Female HEK293 Cells Humans Interleukin-10/immunology Interleukin-12/immunology Interleukin-6/immunology Lymphocyte Activation/immunology Mice Inbred C57BL T-Lymphocytes Helper-Inducer/immunology Th1 Cells/immunology Th2 Cells/immunology Toll-Like Receptor 9/immunology Zinc Finger E-box-Binding Homeobox 1/immunology ChIP-seq RNA-seq Th2 response ZEB1 cDC1 dendritic cells helminth infection immune modulation integrative genomics Immunology and Allergy Original Research Cell Differentiation T-Lymphocytes Helper-Inducer Adoptive Transfer Interleukin-12 Interleukin-10 3. Good health Cell biology medicine.anatomical_structure 030220 oncology & carcinogenesis lcsh:Immunologic diseases. Allergy Epithelial-Mesenchymal Transition Immunology Biology 03 medical and health sciences Th2 Cells Immune system medicine Secretion Epithelial–mesenchymal transition Interleukin-6 Activator (genetics) HEK 293 cells Zinc Finger E-box-Binding Homeobox 1 TLR9 Dendritic Cells Th1 Cells Coculture Techniques 030104 developmental biology Toll-Like Receptor 9 Bone marrow lcsh:RC581-607 |
| Zdroj: | Frontiers in Immunology, Vol 9 (2018) Frontiers in immunology, vol. 9, pp. 2604 Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2018.02604/full |
| Popis: | The role of Epithelial to Mesenchymal Transition (EMT) factor Zeb1 is well defined in metastasis and cancer progression but it's importance in dendritic cells (DCs) is unexplored until now. For the first time we report here that Zeb1 controls immunogenic responses of CD8α + conventional Type-I (cDC1) DCs. We found that ZEB1 expression increases significantly after TLR9 stimulation and its depletion impairs activation, co-stimulation and secretion of important cytokines like IL-6, IL-10 and IL-12 in cDC1 MutuDC line. We further confirmed our findings in primary cDC1 DCs derived from bone marrow. Co-culture of these Zeb1 knock down (KD) DCs with OT-II CD4 + T helper cells skewed their differentiation toward Th2 subtype. Moreover, adoptive transfer of activated Zeb1 KD DCs cleared intestinal worms in helminth infected mice by increasing Th2 responses in vivo. Integrative genomic analysis showed Zeb1 as an activator of immune response genes in cDC1 MutuDCs as compared to other pathway genes. In addition, differentially regulated genes in Zeb1 KD RNA-seq showed significant enrichment of Th2 activation pathways supporting our in vitro findings. Mechanistically, we showed that decreased IL-12 secreted by Zeb1 KD DCs is the plausible mechanism for increased Th2 differentiation. Collectively our data demonstrate that Zeb1 could be targeted in DCs to modulate T-cell mediated adaptive immune responses. |
| Databáze: | OpenAIRE |
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