Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Lung memory B cells ameliorate Alzheimer’s disease-like pathology in 5×FAD mice through the CXCL12-CXCR4 axis

Acta Pharmacologica Sinica (2025)Cite this article

Abstract

Although most AD-related pathological studies are limited to the brain, increasing evidence has demonstrated the contribution of peripheral immune cells to the pathogenesis of AD. We recently demonstrated that meningeal B cells inhibit β-amyloid (Aβ) production in the frontal cortex of young 5×FAD mice. In this study, we explored the precise origin of meningeal B cells. We observed that the AD-like pathology in 5×FAD mice was exacerbated when the germinal center in the lung lymph nodes was specifically destroyed via the intratracheal instillation of anti-CD40 antibodies, whereas it was alleviated via the intratracheal instillation of AAV-mBAFF to overexpress B-cell activating factor in the lungs. We demonstrated that Aβ was drained from the brain via meningeal lymphatics and eventually traveled to the lungs, where it activated B cells via the TLR4/NF-ĸB signaling pathway, whereas the CXCL12-CXCR4 axis regulated lung B-cell infiltration into the frontal cortex. We revealed that the increased number of B cells in the lungs of 5×FAD mice mainly included memory B (Bmem) cells. The supplementation of lung Bmem cells mitigated AD-like pathology in B-cell-deficient μMT-/-/5×FAD mice, which was abolished by using a CXCR4 antagonist. The suppression of CXCL12 expression in frontal microglia via AAV-siCXCL12 inhibited the infiltration of CXCR4+ Bmem cells and increased the Aβ burden in the frontal cortex of 5×FAD mice. Collectively, our results demonstrate an unexpected protective effect of lung Bmem cells on AD-like pathology.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: An increase in lung B cells migrated to the meninges and frontal cortex of 5×FAD mice.
Fig. 2: B cells migrating into the brain delayed AD-like pathology.
Fig. 3: Repeated exogenous Aβ1-42 stimulation or brain-derived Aβ induced the activation of TLR4-NFκB signaling in lung B cells.
Fig. 4: Microglia-derived CXCL12 recruited CXCR4+ B cells to the frontal cortex.
Fig. 5: An increase in Bmem cells was observed in the meninges, frontal cortex, and lungs of 3-month-old 5×FAD mice, and Bmem supplementation reversed cognitive dysfunction and Aβ deposition in 7.5-month-old 5×FAD mice.
Fig. 6: The drainage of Aβ1-42 from the brain to the lungs facilitated the migration of lung Bmem cells into the frontal cortex.
Fig. 7: The CXCR4 antagonist negated the beneficial effects of lung Bmem cell supplementation on AD-like pathology in μMT-/-/5×FAD mice.

Similar content being viewed by others

References

  1. Long JM, Holtzman DM. Alzheimer disease: an update on pathobiology and treatment strategies. Cell. 2019;179:312–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chen X, Holtzman DM. Emerging roles of innate and adaptive immunity in Alzheimer’s disease. Immunity. 2022;55:2236–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Huang LT, Zhang CP, Wang YB, Wang JH. Association of peripheral blood cell profile with Alzheimer’s disease: a meta-analysis. Front Aging Neurosci. 2022;14:888946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Song L, Yang YT, Guo Q, Consortium ZIB, Zhao XM. Cellular transcriptional alterations of peripheral blood in Alzheimer’s disease. BMC Med. 2022;20:266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bulati M, Buffa S, Martorana A, Gervasi F, Camarda C, Azzarello DM, et al. Double negative (IgG+IgD-CD27-) B cells are increased in a cohort of moderate-severe Alzheimer’s disease patients and show a pro-inflammatory trafficking receptor phenotype. J Alzheimers Dis. 2015;44:1241–51.

    Article  CAS  PubMed  Google Scholar 

  6. Kim K, Wang X, Ragonnaud E, Bodogai M, Illouz T, DeLuca M, et al. Therapeutic B-cell depletion reverses progression of Alzheimer’s disease. Nat Commun. 2021;12:2185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Feng W, Zhang Y, Ding S, Chen S, Wang T, Wang Z, et al. B lymphocytes ameliorate Alzheimer’s disease-like neuropathology via interleukin-35. Brain Behav Immun. 2023;108:16–31.

    Article  CAS  PubMed  Google Scholar 

  8. Fitzpatrick Z, Frazer G, Ferro A, Clare S, Bouladoux N, Ferdinand J, et al. Gut-educated IgA plasma cells defend the meningeal venous sinuses. Nature. 2020;587:472–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Brioschi S, Wang WL, Peng V, Wang M, Shchukina I, Greenberg ZJ, et al. Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders. Science. 2021;373:eabf9277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Janssens R, Struyf S, Proost P. Pathological roles of the homeostatic chemokine CXCL12. Cytokine Growth Factor Rev. 2018;44:51–68.

    Article  CAS  PubMed  Google Scholar 

  11. Schropp V, Chunder R, Dietel B, Tacke S, Kuerten S. The presence of cerebellar B cell aggregates is associated with a specific chemokine profile in the cerebrospinal fluid in a mouse model of multiple sclerosis. J Neuroinflammation. 2023;20:18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lee Y, Choi Y, Park EJ, Kwon S, Kim H, Lee JY, et al. Improvement of glymphatic-lymphatic drainage of beta-amyloid by focused ultrasound in Alzheimer’s disease model. Sci Rep. 2020;10:16144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chuang JZ, Yang N, Nakajima N, Otsu W, Fu C, Yang HH, et al. Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration. Nat Commun. 2022;13:374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wang H, Leigh J. Effects of nitric oxide synthase inhibitor omega-nitro-L-arginine methyl ester, on silica-induced inflammatory reaction and apoptosis. Part Fibre Toxicol. 2006;3:14.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Li Q, Chen Y, Feng W, Cai J, Gao J, Ge F, et al. Drainage of senescent astrocytes from brain via meningeal lymphatic routes. Brain Behav Immun. 2022;103:85–96.

    Article  CAS  PubMed  Google Scholar 

  16. Smyth LCD, Xu D, Okar SV, Dykstra T, Rustenhoven J, Papadopoulos Z, et al. Identification of direct connections between the dura and the brain. Nature. 2024;627:165–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schalbetter SM, von Arx AS, Cruz-Ochoa N, Dawson K, Ivanov A, Mueller FS, et al. Adolescence is a sensitive period for prefrontal microglia to act on cognitive development. Sci Adv. 2022;8:eabi6672.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yardeni T, Eckhaus M, Morris HD, Huizing M, Hoogstraten-Miller S. Retro-orbital injections in mice. Lab Anim. 2011;40:155–60.

    Article  Google Scholar 

  19. Yang Z, Wang W, Zhao L, Wang X, Gimple RC, Xu L, et al. Plasma cells shape the mesenchymal identity of ovarian cancers through transfer of exosome-derived microRNAs. Sci Adv. 2021;7:eabb0737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wei SY, Wu TT, Huang JQ, Kang ZP, Wang MX, Zhong YB, et al. Curcumin alleviates experimental colitis via a potential mechanism involving memory B cells and Bcl-6-Syk-BLNK signaling. World J Gastroenterol. 2022;28:5865–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang QT, Wu YJ, Huang B, Ma YK, Song SS, Zhang LL, et al. Etanercept attenuates collagen-induced arthritis by modulating the association between BAFFR expression and the production of splenic memory B cells. Pharmacol Res. 2013;68:38–45.

    Article  CAS  PubMed  Google Scholar 

  22. Sarvaria A, Madrigal JA, Saudemont A. B cell regulation in cancer and anti-tumor immunity. Cell Mol Immunol. 2017;14:662–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Min S, Tao W, Miao Y, Li Y, Wu T, He X, et al. Dual delivery of tetramethylpyrazine and miR-194-5p using soft mesoporous organosilica nanoparticles for acute lung injury therapy. Int J Nanomed. 2023;18:6469–86.

    Article  CAS  Google Scholar 

  24. Holtmaat A, Bonhoeffer T, Chow DK, Chuckowree J, De Paola V, Hofer SB, et al. Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window. Nat Protoc. 2009;4:1128–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Tong L, Han SS, Xue Y, Chen MG, Chen FY, Ke W, et al. Single cell optogenetic stimulation by two-photon excitation fluorescence transfer. iScience. 2023;26:107857.

  26. Mestre H, Hablitz LM, Xavier AL, Feng W, Zou W, Pu T, et al. Aquaporin-4-dependent glymphatic solute transport in the rodent brain. Elife. 2018;7:e40070.

  27. Weber DJ, Gracon AS, Ripsch MS, Fisher AJ, Cheon BM, Pandya PH, et al. The HMGB1-RAGE axis mediates traumatic brain injury-induced pulmonary dysfunction in lung transplantation. Sci Transl Med. 2014;6:252ra124.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Mumaw CL, Levesque S, McGraw C, Robertson S, Lucas S, Stafflinger JE, et al. Microglial priming through the lung-brain axis: the role of air pollution-induced circulating factors. FASEB J. 2016;30:1880–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gregoire C, Spinelli L, Villazala-Merino S, Gil L, Holgado MP, Moussa M, et al. Viral infection engenders bona fide and bystander subsets of lung-resident memory B cells through a permissive mechanism. Immunity. 2022;55:1216–33.e9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mackay F, Browning JL. BAFF: a fundamental survival factor for B cells. Nat Rev Immunol. 2002;2:465–75.

    Article  CAS  PubMed  Google Scholar 

  31. Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, et al. Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci. 2006;26:10129–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Locci A, Orellana H, Rodriguez G, Gottliebson M, McClarty B, Dominguez S, et al. Comparison of memory, affective behavior, and neuropathology in APP(NLGF) knock-in mice to 5xFAD and APP/PS1 mice. Behav Brain Res. 2021;404:113192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kosel F, Torres Munoz P, Yang JR, Wong AA, Franklin TB. Age-related changes in social behaviours in the 5xFAD mouse model of Alzheimer’s disease. Behav Brain Res. 2019;362:160–72.

    Article  CAS  PubMed  Google Scholar 

  34. Da Mesquita S, Louveau A, Vaccari A, Smirnov I, Cornelison RC, Kingsmore KM, et al. Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease. Nature. 2018;560:185–91.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, et al. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018;21:1380–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med. 2012;4:147ra111.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Balczon R, Lin MT, Voth S, Nelson AR, Schupp JC, Wagener BM, et al. Lung endothelium, tau, and amyloids in health and disease. Physiol Rev. 2024;104:533–87.

    Article  CAS  PubMed  Google Scholar 

  38. Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, et al. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol. 2010;11:155–61.

    Article  CAS  PubMed  Google Scholar 

  39. Hua Z, Hou B. TLR signaling in B-cell development and activation. Cell Mol Immunol. 2013;10:103–6.

    Article  CAS  PubMed  Google Scholar 

  40. Lemarquis AL, Einarsdottir HK, Kristjansdottir RN, Jonsdottir I, Ludviksson BR. Transitional B Cells and TLR9 Responses Are Defective in Selective IgA Deficiency. Front Immunol. 2018;9:909.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Shanehbandi D, Majidi J, Kazemi T, Baradaran B, Aghebati-Maleki L. CD20-based immunotherapy of B-cell derived hematologic malignancies. Curr Cancer Drug Targets. 2017;17:423–44.

    Article  CAS  PubMed  Google Scholar 

  42. Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523:337–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Busse M, Michler E, von Hoff F, Dobrowolny H, Hartig R, Frodl T, et al. Alterations in the peripheral immune system in dementia. J Alzheimers Dis. 2017;58:1303–13.

    Article  CAS  PubMed  Google Scholar 

  44. Escott-Price V, Bellenguez C, Wang LS, Choi SH, Harold D, Jones L, et al. Gene-wide analysis detects two new susceptibility genes for Alzheimer’s disease. PLoS ONE. 2014;9:e94661.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Shen P, Fillatreau S. Antibody-independent functions of B cells: a focus on cytokines. Nat Rev Immunol. 2015;15:441–51.

    Article  CAS  PubMed  Google Scholar 

  46. Lefrancais E, Ortiz-Munoz G, Caudrillier A, Mallavia B, Liu F, Sayah DM, et al. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature. 2017;544:105–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wilk MM, Misiak A, McManus RM, Allen AC, Lynch MA, Mills KHG. Lung CD4 tissue-resident memory T cells mediate adaptive immunity induced by previous infection of mice with bordetella pertussis. J Immunol. 2017;199:233–43.

    Article  CAS  PubMed  Google Scholar 

  48. Hosang L, Canals RC, van der Flier FJ, Hollensteiner J, Daniel R, Flugel A, et al. The lung microbiome regulates brain autoimmunity. Nature. 2022;603:138–44.

    Article  CAS  PubMed  Google Scholar 

  49. Odoardi F, Sie C, Streyl K, Ulaganathan VK, Schlager C, Lodygin D, et al. T cells become licensed in the lung to enter the central nervous system. Nature. 2012;488:675–9.

    Article  CAS  PubMed  Google Scholar 

  50. McManus RM, Higgins SC, Mills KH, Lynch MA. Respiratory infection promotes T cell infiltration and amyloid-beta deposition in APP/PS1 mice. Neurobiol Aging. 2014;35:109–21.

    Article  CAS  PubMed  Google Scholar 

  51. Homeyer MA, Falck A, Li LY, Pruss H. From immunobiology to intervention: pathophysiology of autoimmune encephalitis. Semin Immunol. 2025;78:101955.

    Article  CAS  PubMed  Google Scholar 

  52. Machhi J, Yeapuri P, Lu Y, Foster E, Chikhale R, Herskovitz J, et al. CD4+ effector T cells accelerate Alzheimer’s disease in mice. J Neuroinflammation. 2021;18:272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Jain RW, Yong VW. B cells in central nervous system disease: diversity, locations and pathophysiology. Nat Rev Immunol. 2022;22:513–24.

    Article  CAS  PubMed  Google Scholar 

  54. Beck TC, Gomes AC, Cyster JG, Pereira JP. CXCR4 and a cell-extrinsic mechanism control immature B lymphocyte egress from bone marrow. J Exp Med. 2014;211:2567–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Bleul CC, Schultze JL, Springer TA. B lymphocyte chemotaxis regulated in association with microanatomic localization, differentiation state, and B cell receptor engagement. J Exp Med. 1998;187:753–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Klein RS, Rubin JB. Immune and nervous system CXCL12 and CXCR4: parallel roles in patterning and plasticity. Trends Immunol. 2004;25:306–14.

    Article  CAS  PubMed  Google Scholar 

  57. Parachikova A, Cotman CW. Reduced CXCL12/CXCR4 results in impaired learning and is downregulated in a mouse model of Alzheimer disease. Neurobiol Dis. 2007;28:143–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Song ZH, Song XJ, Yang CL, Cao P, Mao Y, Jin Y, et al. Up-regulation of microglial chemokine CXCL12 in anterior cingulate cortex mediates neuropathic pain in diabetic mice. Acta Pharmacol Sin. 2023;44:1337–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Tanabe S, Yamashita T. B-1a lymphocytes promote oligodendrogenesis during brain development. Nat Neurosci. 2018;21:506–16.

    Article  CAS  PubMed  Google Scholar 

  60. Ahn JJ, Islam Y, Clarkson-Paredes C, Karl MT, Miller RH. B cell depletion modulates glial responses and enhances blood vessel integrity in a model of multiple sclerosis. Neurobiol Dis. 2023;187:106290.

    Article  CAS  PubMed  Google Scholar 

  61. Gate D, Saligrama N, Leventhal O, Yang AC, Unger MS, Middeldorp J, et al. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease. Nature. 2020;577:399–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhang Y, Fung ITH, Sankar P, Chen X, Robison LS, Ye L, et al. Depletion of NK cells improves cognitive function in the Alzheimer disease mouse model. J Immunol. 2020;205:502–10.

    Article  CAS  PubMed  Google Scholar 

  63. Marsh SE, Abud EM, Lakatos A, Karimzadeh A, Yeung ST, Davtyan H, et al. The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglial function. Proc Natl Acad Sci USA. 2016;113:E1316–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Yang H, Park SY, Baek H, Lee C, Chung G, Liu X, et al. Adoptive therapy with amyloid-beta specific regulatory T cells alleviates Alzheimer’s disease. Theranostics. 2022;12:7668–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Drieu A, Du S, Storck SE, Rustenhoven J, Papadopoulos Z, Dykstra T, et al. Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid. Nature. 2022;611:585–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Martin F, Chan AC. B cell immunobiology in disease: evolving concepts from the clinic. Annu Rev Immunol. 2006;24:467–96.

    Article  CAS  PubMed  Google Scholar 

  67. Lanzavecchia A. Receptor-mediated antigen uptake and its effect on antigen presentation to class II-restricted T lymphocytes. Annu Rev Immunol. 1990;8:773–93.

    Article  CAS  PubMed  Google Scholar 

  68. Avalos AM, Ploegh HL. Early BCR events and antigen capture, processing, and loading on MHC class II on B cells. Front Immunol. 2014;5:92.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Liu B, Luo W, Huang L, Wei C, Huang X, Liu J, et al. Migration inhibition factor secreted by peripheral blood memory B cells binding to CD74-CD44 receptor complex drives macrophage behavior in Alzheimer’s disease. Am J Alzheimers Dis Other Demen. 2024;39:15333175241238577.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Rosser EC, Mauri C. Regulatory B cells: origin, phenotype, and function. Immunity. 2015;42:607–12.

    Article  CAS  PubMed  Google Scholar 

  71. Dowery R, Benhamou D, Benchetrit E, Harel O, Nevelsky A, Zisman-Rozen S, et al. Peripheral B cells repress B-cell regeneration in aging through a TNF-alpha/IGFBP-1/IGF-1 immune-endocrine axis. Blood. 2021;138:1817–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Gibson LF, Piktel D, Landreth KS. Insulin-like growth factor-1 potentiates expansion of interleukin-7-dependent pro-B cells. Blood. 1993;82:3005–11.

    Article  CAS  PubMed  Google Scholar 

  73. Alvarez XA, Sampedro C, Cacabelos R, Linares C, Aleixandre M, Garcia-Fantini M, et al. Reduced TNF-alpha and increased IGF-I levels in the serum of Alzheimer’s disease patients treated with the neurotrophic agent cerebrolysin. Int J Neuropsychopharmacol. 2009;12:867–72.

    Article  PubMed  Google Scholar 

  74. Heneka MT, Morgan D, Jessen F. Passive anti-amyloid beta immunotherapy in Alzheimer’s disease-opportunities and challenges. Lancet. 2024;404:2198–208.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (82071199, 81970821, 82204365, and 82304466), grants from the Natural Science Foundation of Jiangsu Province (BK20241869), China Postdoctoral Science Foundation (2023T160070 and 2023M740372), and Postdoctoral research funding from Changzhou Medical Center, Nanjing Medical University (CZKYCMCP202302).

Author information

Author notes

  1. These authors contributed equally: Yan-li Zhang, Shi-xin Ding

Authors and Affiliations

  1. Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China

    Yan-li Zhang, Shi-xin Ding, Min Cao, Shu-ying Zhang, Yue Li, Ze Wang, Yu-xi Jin, Si-jia Chen, Yi-miao Wang, Jun-ying Gao, Wei-xi Feng, Ming Xiao & Gang Hu

  2. Brain Institute, Nanjing Brain Hospital, Nanjing Medical University, Nanjing, 210029, China

    Shi-xin Ding, Shu-ying Zhang, Yue Li, Ze Wang, Yu-xi Jin, Si-jia Chen, Yi-miao Wang, Jing-ping Shi, Jun-ying Gao & Ming Xiao

  3. Alice Lloyd College, Pippa Passes, KY, 41844, USA

    Charles Marshall

  4. The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou Second People’s Hospital, Changzhou, 213000, China

    Yin Cao

Authors
  1. Yan-li Zhang
    View author publications

    Search author on:PubMed Google Scholar

  2. Shi-xin Ding
    View author publications

    Search author on:PubMed Google Scholar

  3. Min Cao
    View author publications

    Search author on:PubMed Google Scholar

  4. Shu-ying Zhang
    View author publications

    Search author on:PubMed Google Scholar

  5. Yue Li
    View author publications

    Search author on:PubMed Google Scholar

  6. Ze Wang
    View author publications

    Search author on:PubMed Google Scholar

  7. Yu-xi Jin
    View author publications

    Search author on:PubMed Google Scholar

  8. Si-jia Chen
    View author publications

    Search author on:PubMed Google Scholar

  9. Yi-miao Wang
    View author publications

    Search author on:PubMed Google Scholar

  10. Charles Marshall
    View author publications

    Search author on:PubMed Google Scholar

  11. Jing-ping Shi
    View author publications

    Search author on:PubMed Google Scholar

  12. Jun-ying Gao
    View author publications

    Search author on:PubMed Google Scholar

  13. Wei-xi Feng
    View author publications

    Search author on:PubMed Google Scholar

  14. Yin Cao
    View author publications

    Search author on:PubMed Google Scholar

  15. Ming Xiao
    View author publications

    Search author on:PubMed Google Scholar

  16. Gang Hu
    View author publications

    Search author on:PubMed Google Scholar

Contributions

MX, WXF, and YC conceived and conducted the project. MX, WXF, GH, and YC supervised the project. MX, YLZ, and SXD wrote the paper. YLZ, SXD, MC, SYZ, YL, ZW, and YXJ performed the experiments and data analysis. SXD, SJC, ZW, YMW, and MC contributed to mouse models and cell culture. YLZ, SXD, SJC, JPS, and JYG collected patient tissue samples and information. YLZ, SXD, MC, SYZ, YL, ZW, and YXJ contributed to imaging analysis and interpreted the data.

Corresponding authors

Correspondence to Wei-xi Feng, Yin Cao or Ming Xiao.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Yl., Ding, Sx., Cao, M. et al. Lung memory B cells ameliorate Alzheimer’s disease-like pathology in 5×FAD mice through the CXCL12-CXCR4 axis. Acta Pharmacol Sin (2025). https://doi.org/10.1038/s41401-025-01667-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41401-025-01667-8

Keywords

Search

Advanced search

Quick links