Nicotinamide Suppresses Hyperactivation of Dendritic Cells to Control Autoimmune Disease through PARP Dependent Signaling
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Isolation and Culture
2.2. DC Stimulation
2.3. In Vitro T Cell Activation Assays
2.4. Isolation of Mouse Skin and Draining Lymph Node (DLN) Cells
2.5. Generation of Eα-EGFP Fusion Protein
2.6. Mice
2.7. Flow Cytometry
2.8. ELISA
2.9. RNA Isolation and Gene Expression Profiling
2.10. Gene Set Enrichment Analysis (GSEA)
2.11. Differentially Expressed Genes Analysis
2.12. Correlation Analysis
2.13. Statistical Analysis
3. Results
3.1. NAM, but Not NMN, Inhibits DCs Activation
3.2. NAM Ameliorates the Psoriasis-like Skin Inflammation through Reducing DCs Mediated Immune Response in IMQ-Induced Mouse Model
3.3. NAM Suppresses DCs Activation through PARP Dependent NF-κB Signaling Pathway
3.4. NAMPT Is Activated in DCs of Psoriasis and the NAMPT-PARP Axis Predicts Higher PASI Score
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Wang, A.; Bai, Y. Dendritic cells: The driver of psoriasis. J. Dermatol. 2020, 47, 104–113. [Google Scholar] [CrossRef] [PubMed]
- Ouaaz, F.; Arron, J.; Zheng, Y.; Choi, Y.; Beg, A.A. Dendritic cell development and survival require distinct NF-kappaB subunits. Immunity 2002, 16, 257–270. [Google Scholar] [CrossRef] [PubMed]
- Ganguly, D.; Haak, S.; Sisirak, V.; Reizis, B. The role of dendritic cells in autoimmunity. Nat. Rev. Immunol. 2013, 13, 566–577. [Google Scholar] [CrossRef] [PubMed]
- Guo, C.; You, Z.; Shi, H.; Sun, Y.; Du, X.; Palacios, G.; Guy, C.; Yuan, S.; Chapman, N.M.; Lim, S.A.; et al. SLC38A2 and glutamine signalling in cDC1s dictate anti-tumour immunity. Nature 2023, 620, 200–208. [Google Scholar] [CrossRef] [PubMed]
- Yuan, X.; Duan, Y.; Xiao, Y.; Sun, K.; Qi, Y.; Zhang, Y.; Ahmed, Z.; Moiani, D.; Yao, J.; Li, H.; et al. Vitamin E Enhances Cancer Immunotherapy by Reinvigorating Dendritic Cells via Targeting Checkpoint SHP1. Cancer Discov. 2022, 12, 1742–1759. [Google Scholar] [CrossRef] [PubMed]
- Zhou, X.; Chen, Y.; Cui, L.; Shi, Y.; Guo, C. Advances in the pathogenesis of psoriasis: From keratinocyte perspective. Cell Death Dis. 2022, 13, 81. [Google Scholar] [CrossRef] [PubMed]
- Ni, X.; Lai, Y. Keratinocyte: A trigger or an executor of psoriasis? J. Leukoc. Biol. 2020, 108, 485–491. [Google Scholar] [CrossRef] [PubMed]
- Lowes, M.A.; Suarez-Farinas, M.; Krueger, J.G. Immunology of psoriasis. Annu. Rev. Immunol. 2014, 32, 227–255. [Google Scholar] [CrossRef] [PubMed]
- Denadai, R. The role of plasmacytoid dendritic cells and interferon-alpha in the immunopathogenesis of psoriasis. Indian J. Dermatol. 2013, 58, 247. [Google Scholar] [CrossRef]
- Boehncke, W.H.; Schon, M.P. Psoriasis. Lancet 2015, 386, 983–994. [Google Scholar] [CrossRef]
- Elvehjem, C.A.; Madden, R.J.; Strong, F.M.; Woolley, D.W. The isolation and identification of the anti-black tongue factor. Nutr. Rev. 1974, 32, 48–50. [Google Scholar] [CrossRef] [PubMed]
- Dutta, T.; Kapoor, N.; Mathew, M.; Chakraborty, S.S.; Ward, N.P.; Prieto-Farigua, N.; Falzone, A.; DeLany, J.P.; Smith, S.R.; Coen, P.M.; et al. Source of nicotinamide governs its metabolic fate in cultured cells, mice, and humans. Cell Rep. 2023, 42, 112218. [Google Scholar] [CrossRef] [PubMed]
- Lv, H.; Lv, G.; Chen, C.; Zong, Q.; Jiang, G.; Ye, D.; Cui, X.; He, Y.; Xiang, W.; Han, Q.; et al. NAD+ Metabolism Maintains Inducible PD-L1 Expression to Drive Tumor Immune Evasion. Cell Metab. 2021, 33, 110–127.e5. [Google Scholar] [CrossRef] [PubMed]
- Cichocki, F.; Zhang, B.; Wu, C.Y.; Chiu, E.; Day, A.; O’Connor, R.S.; Yackoubov, D.; Simantov, R.; McKenna, D.H.; Cao, Q.; et al. Nicotinamide enhances natural killer cell function and yields remissions in patients with non-Hodgkin lymphoma. Sci. Transl. Med. 2023, 15, eade3341. [Google Scholar] [CrossRef] [PubMed]
- Namazi, M.R. Nicotinamide: A potential addition to the anti-psoriatic weaponry. FASEB J. 2003, 17, 1377–1379. [Google Scholar] [CrossRef]
- Ungerstedt, J.S.; Blomback, M.; Soderstrom, T. Nicotinamide is a potent inhibitor of proinflammatory cytokines. Clin. Exp. Immunol. 2003, 131, 48–52. [Google Scholar] [CrossRef] [PubMed]
- Yong, L.; Yu, Y.; Li, B.; Ge, H.; Zhen, Q.; Mao, Y.; Yu, Y.; Cao, L.; Zhang, R.; Li, Z.; et al. Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice. Nat. Commun. 2022, 13, 4255. [Google Scholar] [CrossRef] [PubMed]
- Ghimire, T.R. Visualizing Particulate Antigen Targeting to Dendritic Cells (DCs) In vitro. J. Nanomed. Res. 2014, 1, 00007. [Google Scholar] [CrossRef]
- Ghimire, T.R.; Benson, R.A.; Garside, P.; Brewer, J.M. Alum increases antigen uptake, reduces antigen degradation and sustains antigen presentation by DCs in vitro. Immunol. Lett. 2012, 147, 55–62. [Google Scholar] [CrossRef]
- van der Fits, L.; Mourits, S.; Voerman, J.S.; Kant, M.; Boon, L.; Laman, J.D.; Cornelissen, F.; Mus, A.M.; Florencia, E.; Prens, E.P.; et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J. Immunol. 2009, 182, 5836–5845. [Google Scholar] [CrossRef]
- Subramanian, A.; Tamayo, P.; Mootha, V.K.; Mukherjee, S.; Ebert, B.L.; Gillette, M.A.; Paulovich, A.; Pomeroy, S.L.; Golub, T.R.; Lander, E.S.; et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 2005, 102, 15545–15550. [Google Scholar] [CrossRef] [PubMed]
- Liberzon, A.; Subramanian, A.; Pinchback, R.; Thorvaldsdottir, H.; Tamayo, P.; Mesirov, J.P. Molecular signatures database (MSigDB) 3.0. Bioinformatics 2011, 27, 1739–1740. [Google Scholar] [CrossRef] [PubMed]
- Hanzelmann, S.; Castelo, R.; Guinney, J. GSVA: Gene set variation analysis for microarray and RNA-seq data. BMC Bioinform. 2013, 14, 7. [Google Scholar] [CrossRef] [PubMed]
- Charoentong, P.; Finotello, F.; Angelova, M.; Mayer, C.; Efremova, M.; Rieder, D.; Hackl, H.; Trajanoski, Z. Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade. Cell Rep. 2017, 18, 248–262. [Google Scholar] [CrossRef] [PubMed]
- Gentleman, R.C.; Carey, V.J.; Bates, D.M.; Bolstad, B.; Dettling, M.; Dudoit, S.; Ellis, B.; Gautier, L.; Ge, Y.; Gentry, J.; et al. Bioconductor: Open software development for computational biology and bioinformatics. Genome Biol. 2004, 5, R80. [Google Scholar] [CrossRef] [PubMed]
- Huber, W.; Carey, V.J.; Gentleman, R.; Anders, S.; Carlson, M.; Carvalho, B.S.; Bravo, H.C.; Davis, S.; Gatto, L.; Girke, T.; et al. Orchestrating high-throughput genomic analysis with Bioconductor. Nat. Methods 2015, 12, 115–121. [Google Scholar] [CrossRef] [PubMed]
- Michieletto, J.; Delvaux, A.; Chu-Van, E.; Junot, C.; Fenaille, F.; Castelli, F.A. Development of an Untargeted Metabolomics Strategy to Study the Metabolic Rewiring of Dendritic Cells upon Lipopolysaccharide Activation. Metabolites 2023, 13, 311. [Google Scholar] [CrossRef]
- Bonacina, F.; Coe, D.; Wang, G.; Longhi, M.P.; Baragetti, A.; Moregola, A.; Garlaschelli, K.; Uboldi, P.; Pellegatta, F.; Grigore, L.; et al. Myeloid apolipoprotein E controls dendritic cell antigen presentation and T cell activation. Nat. Commun. 2018, 9, 3083. [Google Scholar] [CrossRef] [PubMed]
- Zheng, L.; Szabo, C.; Kern, T.S. Poly(ADP-ribose) polymerase is involved in the development of diabetic retinopathy via regulation of nuclear factor-kappaB. Diabetes 2004, 53, 2960–2967. [Google Scholar] [CrossRef]
- Clark, J.B.; Ferris, G.M.; Pinder, S. Inhibition of nuclear NAD nucleosidase and poly ADP-ribose polymerase activity from rat liver by nicotinamide and 5′-methyl nicotinamide. Biochim. Biophys. Acta 1971, 238, 82–85. [Google Scholar] [CrossRef]
- Smolenska, Z.; Smolenski, R.T.; Zdrojewski, Z. Plasma concentrations of amino acid and nicotinamide metabolites in rheumatoid arthritis--potential biomarkers of disease activity and drug treatment. Biomarkers 2016, 21, 218–224. [Google Scholar] [CrossRef] [PubMed]
- Liang, J.; Han, Z.; Feng, J.; Xie, F.; Luo, W.; Chen, H.; He, J. Targeted metabolomics combined with machine learning to identify and validate new biomarkers for early SLE diagnosis and disease activity. Clin. Immunol. 2024, 264, 110235. [Google Scholar] [CrossRef] [PubMed]
- Kishikawa, T.; Arase, N.; Tsuji, S.; Maeda, Y.; Nii, T.; Hirata, J.; Suzuki, K.; Yamamoto, K.; Masuda, T.; Ogawa, K.; et al. Large-scale plasma-metabolome analysis identifies potential biomarkers of psoriasis and its clinical subtypes. J. Dermatol. Sci. 2021, 102, 78–84. [Google Scholar] [CrossRef] [PubMed]
- Wculek, S.K.; Cueto, F.J.; Mujal, A.M.; Melero, I.; Krummel, M.F.; Sancho, D. Dendritic cells in cancer immunology and immunotherapy. Nat. Rev. Immunol. 2020, 20, 7–24. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Wang, J.; Hong, W.; Zhang, L.; Song, L.; Shi, Q.; Shao, Y.; Hao, G.; Fang, C.; Qiu, Y.; et al. Optineurin modulates the maturation of dendritic cells to regulate autoimmunity through JAK2-STAT3 signaling. Nat. Commun. 2021, 12, 6198. [Google Scholar] [CrossRef]
- Tang, R.; Acharya, N.; Subramanian, A.; Purohit, V.; Tabaka, M.; Hou, Y.; He, D.; Dixon, K.O.; Lambden, C.; Xia, J.; et al. Tim-3 adapter protein Bat3 acts as an endogenous regulator of tolerogenic dendritic cell function. Sci. Immunol. 2022, 7, eabm0631. [Google Scholar] [CrossRef] [PubMed]
- Wu, L.; Hong, X.; Yang, C.; Yang, Y.; Li, W.; Lu, L.; Cai, M.; Cao, D.; Zhuang, G.; Deng, L. Noncanonical MAVS signaling restrains dendritic cell-driven antitumor immunity by inhibiting IL-12. Sci. Immunol. 2023, 8, eadf4919. [Google Scholar] [CrossRef]
- Wu, L.; Yan, Z.; Jiang, Y.; Chen, Y.; Du, J.; Guo, L.; Xu, J.; Luo, Z.; Liu, Y. Metabolic regulation of dendritic cell activation and immune function during inflammation. Front. Immunol. 2023, 14, 1140749. [Google Scholar] [CrossRef] [PubMed]
- Guo, C.; Chi, H. Immunometabolism of dendritic cells in health and disease. Adv. Immunol. 2023, 160, 83–116. [Google Scholar]
- Lappas, M.; Permezel, M. The anti-inflammatory and antioxidative effects of nicotinamide, a vitamin B3 derivative, are elicited by FoxO3 in human gestational tissues: Implications for preterm birth. J. Nutr. Biochem. 2011, 22, 1195–1201. [Google Scholar] [CrossRef]
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Cao, A.-P.; Wang, Y.-Y.; Shen, Y.-Y.; Liu, Y.-H.; Liu, J.-Y.; Wang, Y.; Guo, Y.; Wang, R.-B.; Xie, B.-Y.; Pan, X.; et al. Nicotinamide Suppresses Hyperactivation of Dendritic Cells to Control Autoimmune Disease through PARP Dependent Signaling. Nutrients 2024, 16, 2665. https://doi.org/10.3390/nu16162665
Cao A-P, Wang Y-Y, Shen Y-Y, Liu Y-H, Liu J-Y, Wang Y, Guo Y, Wang R-B, Xie B-Y, Pan X, et al. Nicotinamide Suppresses Hyperactivation of Dendritic Cells to Control Autoimmune Disease through PARP Dependent Signaling. Nutrients. 2024; 16(16):2665. https://doi.org/10.3390/nu16162665
Chicago/Turabian StyleCao, Ai-Ping, Yun-Ying Wang, Yan-Yan Shen, Yan-Hong Liu, Jia-Yu Liu, Yao Wang, Yue Guo, Rui-Bo Wang, Bo-Yang Xie, Xin Pan, and et al. 2024. "Nicotinamide Suppresses Hyperactivation of Dendritic Cells to Control Autoimmune Disease through PARP Dependent Signaling" Nutrients 16, no. 16: 2665. https://doi.org/10.3390/nu16162665