Stock Ticker

B cells modulate lung antiviral inflammatory responses via the neurotransmitter acetylcholine

  • Wu, T. T.-H. et al. Interstitial macrophages are a focus of viral takeover and inflammation in COVID-19 initiation in human lung. J. Exp. Med. 221, e20232192 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ferreira, A. C. et al. Macrophages undergo necroptosis during severe influenza A infection and contribute to virus-associated cytokine storm. Front. Cell Infect. Microbiol. 16, e1067285 (2023).

    Article 

    Google Scholar
     

  • Karki, R. et al. Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell 184, 149–168.e17 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • DeBerge, M. P., Ely, K. H. & Enelow, R. I. Soluble, but not transmembrane, TNF-α is required during influenza infection to limit the magnitude of immune responses and the extent of immunopathology. J. Immunol. 192, 5839–5851 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mestan, J. et al. Antiviral effects of recombinant tumour necrosis factor in vitro. Nature 323, 816–819 (1986).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wong, G. H. W. & Goeddel, D. V. Tumour necrosis factors α and β inhibit virus replication and synergize with interferons. Nature 323, 819–822 (1986).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Blanco-Melo, D. et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell 181, 1036–1045.e9 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Baillie, J. K. & Digard, P. Influenza—time to target the host? N. Engl. J. Med. 369, 191–193 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Serhan, C. N., Chiang, N. & Van Dyke, T. E. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat. Rev. Immunol. 8, 349–361 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • de Jong, M. D. et al. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat. Med. 12, 1203–1207 (2006).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Moore, J. B. & June, C. H. Cytokine release syndrome in severe COVID-19. Science 368, 473–474 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Watanabe, T. et al. Influenza virus–host interactome screen as a platform for antiviral drug development. Cell Host Microbe 16, 795–805 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Weber, G. F. et al. Pleural innate response activator B cells protect against pneumonia via a GM–CSF–IgM axis. J. Exp. Med. 211, 1243–1256 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rauch, P. J. et al. Innate response activator B cells protect against microbial sepsis. Science 335, 597–601 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yanaba, K. et al. A aegulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity 28, 639–650 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Flores-Borja, F. et al. CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci. Transl. Med. 5, 173ra23–173ra23 (2013).

    Article 
    PubMed 

    Google Scholar
     

  • Mauri, C. & Bosma, A. Immune regulatory function of B cells. Annu. Rev. Immunol. 30, 221–241 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rosser, E. C. & Mauri, C. Regulatory B cells: origin, phenotype, and function. Immunity 42, 607–612 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rosser, E. C., Blair, P. A. & Mauri, C. Cellular targets of regulatory B cell-mediated suppression. Mol. Immunol. 62, 296–304 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Horikawa, M. et al. Regulatory B cell (B10 cell) expansion during Listeria infection governs innate and cellular immune responses in mice. J. Immunol. 190, 1158–1168 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Suchanek, O. et al. Tissue-resident B cells orchestrate macrophage polarisation and function. Nat. Commun. 14, 7081 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, S. et al. STING-induced regulatory B cells compromise NK function in cancer immunity. Nature 610, 373–380 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, B., Vogelzang, A. & Fagarasan, S. Secreted immune metabolites that mediate immune cell communication and function. Trends Immunol. 43, 990–1005 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, B. et al. B cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity. Nature 599, 471–476 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shirey, K. A. et al. Novel neuroendocrine role of γ-aminobutyric acid and gastrin-releasing peptide in the host response to influenza infection. Mucosal Immunol. 16, 302–311 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ma, Y., Jun, H. & Wu, J. Immune cell cholinergic signaling in adipose thermoregulation and immunometabolism. Trends Immunol. 43, 718–727 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Reardon, C. et al. Lymphocyte-derived ACh regulates local innate but not adaptive immunity. Proc. Natl Acad. Sci. USA 110, 1410–1415 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nachmansohn, D. & Machado, A. L. The formation of acetylcholine. a new enzyme: ‘choline acetylase’. J. Neurophysiol. 6, 397–403 (1943).

    Article 
    CAS 

    Google Scholar
     

  • Cai, Y. et al. Choline acetyltransferase structure reveals distribution of mutations that cause motor disorders. EMBO J. 23, 2047–2058 (2004).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tansey, E. M. Henry Dale and the discovery of acetylcholine. C. R. Biol. 329, 419–425 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fishman, M. C. Sir Henry Hallett Dale and acetylcholine story. Yale J. Biol. Med 45, 104–118 (1972).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Loewi, O. Über humorale übertragbarkeit der Herznervenwirkung. Pflügers Arch. 189, 239–242 (1921).

    Article 

    Google Scholar
     

  • Feldberg, W. & Guimarāis, J. A. The liberation of acetylcholine by potassium. J. Physiol. 86, 306–314 (1936).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dale, H. H. & Feldberg, W. The chemical transmitter of vagus effects to the stomach. J. Physiol. 81, 320–334 (1934).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, T. et al. The vagus nerve and nicotinic receptors involve inhibition of HMGB1 release and aarly pro-inflammatory cytokines function in collagen-induced arthritis. J. Clin. Immunol. 30, 213–220 (2010).

    Article 
    PubMed 

    Google Scholar
     

  • van Maanen, M. A. et al. Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced arthritis in mice. Arthritis Rheum. 60, 114–122 (2009).

    Article 
    PubMed 

    Google Scholar
     

  • Liu, D. et al. The effect of the cholinergic anti-inflammatory pathway on collagen-induced arthritis involves the modulation of dendritic cell differentiation. Arthritis Res. Ther. 20, 263 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zheng, W. et al. Acetylcholine ameliorates colitis by promoting IL-10 secretion of monocytic myeloid-derived suppressor cells through the nAChR/ERK pathway. Proc. Natl Acad. Sci. 118, e2017762118 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kelly, M. J., Breathnach, C., Tracey, K. J. & Donnelly, S. C. Manipulation of the inflammatory reflex as a therapeutic strategy. C. R. Med 3, 100696 (2022).

    CAS 

    Google Scholar
     

  • Tynan, A., Brines, M. & Chavan, S. S. Control of inflammation using non-invasive neuromodulation: past, present and promise. Int. Immunol. 34, 119–128 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pavlov, V. A. & Tracey, K. J. The vagus nerve and the inflammatory reflex—linking immunity and metabolism. Nat. Rev. Endocrinol. 8, 743–754 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lei, W. & Duan, Z. Advances in the treatment of cholinergic anti-inflammatory pathways in gastrointestinal diseases by electrical stimulation of vagus nerve. Digestion 102, 128–138 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Pavlov, V. A., Chavan, S. S. & Tracey, K. J. Molecular and functional neuroscience in immunity. Annu. Rev. Immunol. 36, 783–812 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Caravaca, A. S. et al. Vagus nerve stimulation promotes resolution of inflammation by a mechanism that involves Alox15 and requires the α7nAChR subunit. Proc. Natl Acad. Sci. USA 119, e2023285119 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Koopman, F. A. et al. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc. Natl Acad. Sci. USA 113, 8284–8289 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pavlov, V. A. & Tracey, K. J. Bioelectronic medicine: Preclinical insights and clinical advances. Neuron 110, 3627–3644 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Falvey, A., Metz, C. N., Tracey, K. J. & Pavlov, V. A. Peripheral nerve stimulation and immunity: the expanding opportunities for providing mechanistic insight and therapeutic intervention. Int. Immunol. 34, 107–118 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bonaz, B. et al. Chronic vagus nerve stimulation in Crohn’s disease: a 6-month follow-up pilot study. Neurogastroenterol. Motil. 28, 948–953 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sinniger, V. et al. A 12-month pilot study outcomes of vagus nerve stimulation in Crohn’s disease. Neurogastroenterol. Motil. 32, e13911 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jiang, W. et al. Acetylcholine-producing NK cells attenuate CNS inflammation via modulation of infiltrating monocytes/macrophages. Proc. Natl Acad. Sci. USA 114, E6202–E6211 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rosas-Ballina, M. et al. Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science 334, 98–101 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Olofsson, P. S. et al. Blood pressure regulation by CD4+ lymphocytes expressing choline acetyltransferase. Nat. Biotechnol. 34, 1066–1071 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ramirez, V. T. et al. T-cell derived acetylcholine aids host defenses during enteric bacterial infection with Citrobacter rodentium. PLoS Pathog. 15, e1007719 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cox, M. A. et al. Choline acetyltransferase-expressing T cells are required to control chronic viral infection. Science 363, 639–644 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chu, C. et al. The ChAT-acetylcholine pathway promotes group 2 innate lymphoid cell responses and anti-helminth immunity. Sci. Immunol. 6, eabe3218 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Roberts, L. B. et al. Acetylcholine production by group 2 innate lymphoid cells promotes mucosal immunity to helminths. Sci. Immunol. 6, eabd0359 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Shapira, S. D. et al. A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection. Cell 139, 1255–1267 (2009).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Savage, H. P. et al. TLR induces reorganization of the IgM-BCR complex regulating murine B-1 cell responses to infections. eLife 8, e46997 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ghoneim, H. E., Thomas, P. G. & McCullers, J. A. Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections. J. Immunol. 191, 1250–1259 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Liao, M. et al. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat. Med. 26, 842–844 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Malainou, C., Abdin, S. M., Lachmann, N., Matt, U. & Herold, S. Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting. J. Clin. Invest. 133, e170501 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Whitsett, J. A. & Weaver, T. E. Hydrophobic surfactant proteins in lung function and disease. N. Engl. J. Med. 347, 2141–2148 (2002).

    Article 
    PubMed 

    Google Scholar
     

  • Veldhuizen, E. J. A. & Haagsman, H. P. Role of pulmonary surfactant components in surface film formation and dynamics. Biochim. Biophys. Acta Biomembranes 1467, 255–270 (2000).

    Article 
    CAS 

    Google Scholar
     

  • Wei, X., Narasimhan, H., Zhu, B. & Sun, J. Host recovery from respiratory viral infection. Annu. Rev. Immunol. 41, 277–300 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Narasimhan, H., Wu, Y., Goplen, N. P. & Sun, J. Immune determinants of chronic sequelae after respiratory viral infection. Sci. Immunol. 7, eabm7996 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ochsenbein, A. F. et al. Control of early viral and bacterial distribution and disease by natural antibodies. Science 286, 2156–2159 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Baumgarth, N. et al. B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection. J. Exp. Med. 192, 271–280 (2000).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schloss, M. J. et al. B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis. Nat. Immunol. 23, 605–618 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Becher, B., Waisman, A. & Lu, L.-F. Conditional gene-targeting in mice: problems and solutions. Immunity 48, 835–836 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhao, Y. et al. Altered phenotype and enhanced antibody-producing ability of peripheral B cells in mice with Cd19-driven Cre expression. Cells 11, 700 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nguyen, T. T. T. et al. The IgM receptor FcμR limits tonic BCR signaling by regulating expression of the IgM BCR. Nat. Immunol. 18, 321–333 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Savage, H. P. et al. Blimp-1-dependent and -independent natural antibody production by B-1 and B-1-derived plasma cells. J. Exp. Med. 214, 2777–2794 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Woznicki, J. A. et al. TNF-α synergises with IFN-γ to induce caspase-8-JAK1/2-STAT1-dependent death of intestinal epithelial cells. Cell Death Dis. 12, 1–15 (2021).

    Article 

    Google Scholar
     

  • Oyler-Yaniv, J., Oyler-Yaniv, A., Maltz, E. & Wollman, R. TNF controls a speed-accuracy tradeoff in the cell death decision to restrict viral spread. Nat. Commun. 12, 2992 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Matsumoto, R. et al. Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity. Nat. Immunol. 24, 1370–1381 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Swanson, R. V. et al. Antigen-specific B cells direct T follicular-like helper cells into lymphoid follicles to mediate Mycobacterium tuberculosis control. Nat. Immunol. 24, 855–868 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Czura, C. J., Friedman, S. G. & Tracey, K. J. Neural inhibition of inflammation: the cholinergic anti-inflammatory pathway. J. Endotoxin Res. 9, 409–413 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, H. et al. Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation. Nature 421, 384–388 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, H. et al. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat. Med. 10, 1216–1221 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ulloa, L. The vagus nerve and the nicotinic anti-inflammatory pathway. Nat. Rev. Drug Discov. 4, 673–684 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Borovikova, L. V. et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405, 458–462 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yoshikawa, H. et al. Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-κB phosphorylation and nuclear factor-κB transcriptional activity through nicotinic acetylcholine receptor α7. Clin. Exp. Immunol. 146, 116–123 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • de Jonge, W. J. et al. Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat. Immunol. 6, 844–851 (2005).

    Article 
    PubMed 

    Google Scholar
     

  • Pandey, P. & Karupiah, G. Targeting tumour necrosis factor to ameliorate viral pneumonia. FEBS J. 289, 883–900 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Peper, R. L. & Van Campen, H. Tumor necrosis factor as a mediator of inflammation in influenza A viral pneumonia. Microb. Pathog. 19, 175–183 (1995).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Salomon, R., Hoffmann, E. & Webster, R. G. Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection. Proc. Natl Acad. Sci. USA 104, 12479–12481 (2007).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mettelman, R. C. et al. Baseline innate and T cell populations are correlates of protection against symptomatic influenza virus infection independent of serology. Nat. Immunol. 24, 1511–1526 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, F.-F. et al. GM-CSF in the Lung Protects against Lethal Influenza Infection. Am. J. Respir. Crit. Care Med. 184, 259–268 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sever-Chroneos, Z. et al. GM-CSF modulates pulmonary resistance to influenza A infection. Antiviral Res. 92, 319–328 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Halstead, E. S. et al. GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization. Respir. Res. 19, 3 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rabin, R. C. Breakthrough drug for COVID-19 may be risky for mild cases. The New York Times. 24 June 2020; updated, 2 September (2020).

  • WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA 324, 1330–1341 (2020).

    Article 

    Google Scholar
     

  • Li, H., Yan, B., Gao, R., Ren, J. & Yang, J. Effectiveness of corticosteroids to treat severe COVID-19: a systematic review and meta-analysis of prospective studies. Int. Immunopharmacol. 100, 108121 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • RECOVERY Collaborative Groupet al. Dexamethasone in Hospitalized Patients with Covid-19. N. Engl. J. Med. 384, 693–704 (2021).

    Article 

    Google Scholar
     

  • Crothers, K. et al. Dexamethasone in hospitalised COVID-19 patients not on intensive respiratory support. Eur. Respir. J. 60, 2102532 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Covello, R. D. et al. Meta-analysis of glucocorticoids for Covid-19 patients not receiving oxygen. NEJM Evid. 2, EVIDoa2200283 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Shang, L., Zhao, J., Hu, Y., Du, R. & Cao, B. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet 395, 683–684 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Russell, C. D., Millar, J. E. & Baillie, J. K. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 395, 473–475 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kopf, M., Schneider, C. & Nobs, S. P. The development and function of lung-resident macrophages and dendritic cells. Nat. Immunol. 16, 36–44 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Park, M. D., Silvin, A., Ginhoux, F. & Merad, M. Macrophages in health and disease. Cell 185, 4259–4279 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Aegerter, H., Lambrecht, B. N. & Jakubzick, C. V. Biology of lung macrophages in health and disease. Immunity 55, 1564–1580 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Morris, D. L. & Rothstein, T. L. Abnormal transcription factor induction through the surface immunoglobulin M receptor of B-1 lymphocytes. J. Exp. Med. 177, 857–861 (1993).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Benschop, R. J., Melamed, D., Nemazee, D. & Cambier, J. C. Distinct signal thresholds for the unique antigen receptor–linked gene expression programs in mature and immature B cells. J. Exp. Med. 190, 749–756 (1999).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Russell, D. M. et al. Peripheral deletion of self-reactive B cells. Nature 354, 308–311 (1991).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Goodnow, C. C. et al. Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature 334, 676–682 (1988).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Radomir, L. et al. The survival and function of IL-10-producing regulatory B cells are negatively controlled by SLAMF5. Nat. Commun. 12, 1893 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mauri, C. Novel frontiers in regulatory B cells. Immunol. Rev. 299, 5–9 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Matsumoto, M. et al. Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation. Immunity 41, 1040–1051 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fillatreau, S. Natural regulatory plasma cells. Curr. Opin. Immunol. 55, 62–66 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shen, P. et al. IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature 507, 366–370 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shirey, K. A. et al. Novel role of gastrin releasing peptide-mediated signaling in the host response to influenza infection. Mucosal Immunol. 12, 223–231 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tracey, K. J. The inflammatory reflex. Nature 420, 853–859 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Matthay, M. A. & Ware, L. B. Can nicotine treat sepsis? Nat. Med. 10, 1161–1162 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Vukelic, M., Qing, X., Redecha, P., Koo, G. & Salmon, J. E. Cholinergic receptors modulate immune complex-induced inflammation in vitro and in vivo. J. Immunol. 191, 1800–1807 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nakamura, Y. et al. Alpha 7 nicotinic acetylcholine receptors signaling boosts cell-cell interactions in macrophages effecting anti-inflammatory and organ protection. Commun. Biol. 6, 1–15 (2023).

    Article 

    Google Scholar
     

  • Doucett, V. P. et al. Enumeration and characterization of virus-specific B cells by multicolor flow cytometry. J. Immunol. Methods 303, 40–52 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Stuart, T., Srivastava, A., Madad, S., Lareau, C. A. & Satija, R. Single-cell chromatin state analysis with Signac. Nat. Methods 18, 1333–1341 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587.e29 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289–1296 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Korotkevich, G. et al. Fast gene set enrichment analysis. Preprint at bioRxiv https://doi.org/10.1101/060012 (2021).

  • Liberzon, A. et al. Molecular signatures database (MSigDB) 3.0. Bioinformatics 27, 1739–1740 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cherry, C. et al. Computational reconstruction of the signalling networks surrounding implanted biomaterials from single-cell transcriptomics. Nat. Biomed. Eng. 5, 1228–1238 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Andreatta, M. & Carmona, S. J. UCell: robust and scalable single-cell gene signature scoring. Comput. Struct. Biotechnol. J. 19, 3796–3798 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32, 2847–2849 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gu, Z., Gu, L., Eils, R., Schlesner, M. & Brors, B. Circlize implements and enhances circular visualization in R. Bioinformatics 30, 2811–2812 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Christensen, A. D., Skov, S., Kvist, P. H. & Haase, C. Depletion of regulatory T cells in a hapten-induced inflammation model results in prolonged and increased inflammation driven by T cells. Clin. Exp. Immunol. 179, 485–499 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Grinberg-Bleyer, Y. et al. Cutting edge: NF-κB p65 and c-Rel control epidermal development and immune homeostasis in the skin. J. Immunol. 194, 2472–2476 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Shaabani, N. et al. The probacterial effect of type I interferon signaling requires its own negative regulator USP18. Sci. Immunol. 3, eaau2125 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schweiger, B., Zadow, I., Heckler, R., Timm, H. & Pauli, G. Application of a fluorogenic PCR assay for typing and subtyping of influenza viruses in respiratory samples. J. Clin. Microbiol. 38, 1552–1558 (2000).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Smith, F. L. et al. B-1 plasma cells require non-cognate CD4 T cell help to generate a unique repertoire of natural IgM. J. Exp. Med. 220, e20220195 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Source link

    Get RawNews Daily

    Stay informed with our RawNews daily newsletter email

    Liverpool defender left out of World Cup squad

    Madonna Covering Rent For Musicians Working At Her Old NYC Rehearsal Space

    Up 16.5%! Here’s why Hollywood Bowl stock smashed the FTSE 250 today

    Trump says Iran would not get sanctions relief in exchange for giving up enriched uranium