Laponite Lights Calcium Flickers by Reprogramming Lysosomes to Steer Dc Migration for An Effective Antiviral CD8+ T-Cell Response.

Immunotherapy using dendritic cell (DC)-based vaccination is an established approach for treating cancer and infectious diseases; however, its efficacy is limited. Therefore, targeting the restricted migratory capacity of the DCs may enhance their therapeutic efficacy. In this study, the effect of laponite (Lap) on DCs, which can be internalized into lysosomes and induce cytoskeletal reorganization via the lysosomal reprogramming-calcium flicker axis, is evaluated, and it is found that Lap dramatically improves the in vivo homing ability of these DCs to lymphoid tissues. In addition, Lap improves antigen cross-presentation by DCs and increases DC-T-cell synapse formation, resulting in enhanced antigen-specific CD8+ T-cell activation. Furthermore, a Lap-modified cocktail (Lap@cytokine cocktail [C-C]) is constructed based on the gold standard, C-C, as an adjuvant for DC vaccines. Lap@C-C-adjuvanted DCs initiated a robust cytotoxic T-cell immune response against hepatitis B infection, resulting in > 99.6% clearance of viral DNA and successful hepatitis B surface antigen seroconversion. These findings highlight the potential value of Lap as a DC vaccine adjuvant that can regulate DC homing, and provide a basis for the development of effective DC vaccines.

[1]  R. Ahrends,et al.  High-throughput assessment identifying major platelet Ca2+ entry pathways via tyrosine kinase-linked and G protein-coupled receptors. , 2023, Cell calcium.

[2]  Zhe Li,et al.  A Controlled Biodegradable Triboelectric Nanogenerator Based on PEGDA/Laponite Hydrogels. , 2023, ACS applied materials & interfaces.

[3]  Y. Lim,et al.  A nanoadjuvant that dynamically coordinates innate immune stimuli activation enhances cancer immunotherapy and reduces immune cell exhaustion , 2023, Nature Nanotechnology.

[4]  Gang Liu,et al.  Connecting Calcium-Based Nanomaterials and Cancer: From Diagnosis to Therapy , 2022, Nano-Micro Letters.

[5]  Yasuyuki Fujita,et al.  Calcium sparks enhance the tissue fluidity within epithelial layers and promote apical extrusion of transformed cells. , 2022, Cell reports.

[6]  L. Shultz,et al.  Lung fibroblasts facilitate pre-metastatic niche formation by remodeling the local immune microenvironment. , 2022, Immunity.

[7]  Yiyang Guo,et al.  Virus-Like Particle-Templated Silica-Adjuvanted Nanovaccines with Enhanced Humoral and Cellular Immunity. , 2022, ACS nano.

[8]  Wanlu Du,et al.  Parkinson’s disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes , 2022, Cell.

[9]  H. Ploegh,et al.  A guide to antigen processing and presentation , 2022, Nature Reviews Immunology.

[10]  L. Diehl,et al.  Multi-parametric analysis of human livers reveals variation in intrahepatic inflammation across phases of chronic hepatitis B infection. , 2022, Journal of hepatology.

[11]  Marisierra Espinar-Buitrago,et al.  New Approaches to Dendritic Cell-Based Therapeutic Vaccines Against HIV-1 Infection , 2022, Frontiers in Immunology.

[12]  A. Da'dara,et al.  Schistosome immunomodulators , 2021, PLoS pathogens.

[13]  C. Halin,et al.  Imaging leukocyte migration through afferent lymphatics , 2021, Immunological reviews.

[14]  Linsheng Zhan,et al.  Large‐Sized Graphene Oxide Nanosheets Increase DC–T‐Cell Synaptic Contact and the Efficacy of DC Vaccines against SARS‐CoV‐2 , 2021, Advanced materials.

[15]  Xuetao Cao,et al.  Dendritic cell migration in inflammation and immunity , 2021, Cellular & Molecular Immunology.

[16]  G. Cappellano,et al.  Nano-Microparticle Platforms in Developing Next-Generation Vaccines , 2021, Vaccines.

[17]  J. Parrington,et al.  Deciphering the Role of Endolysosomal Ca2+ Channels in Immunity , 2021, Frontiers in Immunology.

[18]  M. Naghizadeh,et al.  Kinetics of activation marker expression after in vitro polyclonal stimulation of chicken peripheral T cells , 2021, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[19]  S. Etienne-Manneville,et al.  Cytoskeletal Crosstalk in Cell Migration. , 2020, Trends in cell biology.

[20]  E. Paluch,et al.  Of Cell Shapes and Motion: The Physical Basis of Animal Cell Migration. , 2020, Developmental cell.

[21]  B. Kong,et al.  Dendritic cells as cancer therapeutics. , 2019, Seminars in cell & developmental biology.

[22]  Neelam,et al.  Laponite-based Nanomaterials for Biomedical Applications: A Review. , 2019, Current pharmaceutical design.

[23]  J. Sáez,et al.  Role of calcium permeable channels in dendritic cell migration. , 2018, Current opinion in immunology.

[24]  S. Kottilil,et al.  Chronic Hepatitis B Infection: A Review , 2018, JAMA.

[25]  Xiaojun Zhou,et al.  Impact of bone marrow mesenchymal stem cell immunomodulation on the osteogenic effects of laponite , 2018, Stem Cell Research & Therapy.

[26]  A. Ballabio,et al.  Lysosome signaling controls the migration of dendritic cells , 2017, Science Immunology.

[27]  F. Sánchez‐Madrid,et al.  CD69: from activation marker to metabolic gatekeeper , 2017, European journal of immunology.

[28]  João Rodrigues,et al.  Laponite®: A key nanoplatform for biomedical applications? , 2017, Nanomedicine : nanotechnology, biology, and medicine.

[29]  Nina Bhardwaj,et al.  Dendritic cell-based immunotherapy , 2016, Cell Research.

[30]  R. Förster,et al.  Dendritic cell migration in health and disease , 2016, Nature Reviews Immunology.

[31]  J. Pittman,et al.  Ca2+/H+ exchange by acidic organelles regulates cell migration in vivo. , 2016, The Journal of cell biology.

[32]  F. Benvenuti The Dendritic Cell Synapse: A Life Dedicated to T Cell Activation , 2016, Front. Immunol..

[33]  A. P. Bell,et al.  Proinflammatory Effects of Pyrogenic and Precipitated Amorphous Silica Nanoparticles in Innate Immunity Cells. , 2016, Toxicological sciences : an official journal of the Society of Toxicology.

[34]  R. Nixon,et al.  Presenilin 1 Maintains Lysosomal Ca(2+) Homeostasis via TRPML1 by Regulating vATPase-Mediated Lysosome Acidification. , 2015, Cell reports.

[35]  S. Akira,et al.  Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production , 2015, European journal of immunology.

[36]  R. Oreffo,et al.  Clay: New Opportunities for Tissue Regeneration and Biomaterial Design , 2013, Advanced materials.

[37]  J. Neefjes,et al.  Towards a systems understanding of MHC class I and MHC class II antigen presentation , 2011, Nature Reviews Immunology.

[38]  Zhi-Yong Wang,et al.  The regulation of CD4+ T cell immune responses toward Th2 cell development by prostaglandin E2. , 2011, International immunopharmacology.

[39]  R. Binda,et al.  Hepatitis B virus surface antigen impairs myeloid dendritic cell function: a possible immune escape mechanism of hepatitis B virus , 2009, Immunology.

[40]  M. Albert,et al.  A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation. , 2005, Blood.

[41]  G. Gerken,et al.  Hepatitis B virus‐induced defect of monocyte‐derived dendritic cells leads to impaired T helper type 1 response in vitro: mechanisms for viral immune escape , 2003, Immunology.

[42]  R. Förster,et al.  Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells. , 2002, Blood.

[43]  A. Enk,et al.  Pro‐inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum‐free conditions , 1997, European journal of immunology.

[44]  Haoxing Xu,et al.  Lysosomal physiology. , 2015, Annual review of physiology.

[45]  E. Aktas,et al.  Relationship between CD107a expression and cytotoxic activity. , 2009, Cellular immunology.