{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:26:10Z","timestamp":1793089570652,"version":"4.5.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Na\u00efve T (Tn) cells require two homeostatic signals for long-term survival: tonic T cell receptor:self-peptide\u2013MHC contact and IL-7 stimulation. However, how microbial exposure impacts Tn homeostasis is still unclear. Here we show that infections can lead to the expansion of a subpopulation of long-lived, Ly6C<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> Tn cells with accelerated effector function. Mechanistically, mono-infection with West Nile virus transiently, and polymicrobial exposure persistently, enhances Ly6C expression selectively on CD5<jats:sup>hi<\/jats:sup>CD8<jats:sup>+<\/jats:sup> cells, which in the case of polyinfection translates into a numerical CD8<jats:sup>+<\/jats:sup> Tn cell increase in the lymph nodes. This conversion and expansion of Ly6C<jats:sup>+<\/jats:sup> Tn cells depends on IFN-I, which upregulates MHC class I expression and enhances tonic TCR signaling in differentiating Tn cells. Moreover, for Ly6C<jats:sup>+<\/jats:sup>CD8<jats:sup>+\u2009<\/jats:sup>Tn cells, IFN-I-mediated signals optimize their homing to secondary sites, extend their lifespan, and enhance their effector differentiation and antibacterial function, particularly for low-affinity clones. Our results thus uncover significant regulation of Tn homeostasis and function via infection-driven IFN-I, with potential implications for immunotherapy.<\/jats:p>","DOI":"10.1038\/s41467-021-25645-w","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T10:04:08Z","timestamp":1630922648000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Infection-induced type I interferons critically modulate the homeostasis and function of CD8+ na\u00efve T cells"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7630-1219","authenticated-orcid":false,"given":"Mladen","family":"Jergovi\u0107","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Coplen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7745-0179","authenticated-orcid":false,"given":"Jennifer L.","family":"Uhrlaub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Besselsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan J.","family":"Smithey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5830-5323","authenticated-orcid":false,"given":"Janko","family":"Nikolich-\u017dugich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"25645_CR1","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1046\/j.1365-2567.2002.01447.x","volume":"106","author":"M Berard","year":"2002","unstructured":"Berard, M. & Tough, D. F. Qualitative differences between na\u00efve and memory T cells. Immunology 106, 127\u2013138 (2002).","journal-title":"Immunology"},{"key":"25645_CR2","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/nri1292","volume":"4","author":"J Nikolich-\u017dugich","year":"2004","unstructured":"Nikolich-\u017dugich, J., Slifka, M. K. & Messaoudi, I. The many important facets of T-cell repertoire diversity. Nat. Rev. Immunol. 4, 123\u2013132 (2004).","journal-title":"Nat. Rev. Immunol."},{"key":"25645_CR3","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/nri2657","volume":"9","author":"K Takada","year":"2009","unstructured":"Takada, K. & Jameson, S. C. Naive T cell homeostasis: from awareness of space to a sense of place. Nat. Rev. Immunol. 9, 823\u2013832 (2009).","journal-title":"Nat. Rev. Immunol."},{"key":"25645_CR4","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1038\/ni.2018","volume":"12","author":"J Sprent","year":"2011","unstructured":"Sprent, J. & Surh, C. D. Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells. Nat. Immunol. 12, 478\u2013484 (2011).","journal-title":"Nat. Immunol."},{"key":"25645_CR5","doi-asserted-by":"publisher","first-page":"3158LP","DOI":"10.4049\/jimmunol.174.6.3158","volume":"174","author":"WC Kieper","year":"2005","unstructured":"Kieper, W. C. et al. Cutting edge: recent immune status determines the source of antigens that drive homeostatic T cell expansion. J. Immunol. 174, 3158LP\u20133163LP (2005).","journal-title":"J. Immunol."},{"key":"25645_CR6","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1038\/nature17655","volume":"532","author":"LK Beura","year":"2016","unstructured":"Beura, L. K. et al. Normalizing the environment recapitulates adult human immune traits in laboratory mice. Nature 532, 512\u2013516 (2016).","journal-title":"Nature"},{"key":"25645_CR7","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1038\/ni.3483","volume":"17","author":"V Pulko","year":"2016","unstructured":"Pulko, V. et al. Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses. Nat. Immunol. 17, 966\u2013975 (2016).","journal-title":"Nat. Immunol."},{"key":"25645_CR8","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.1084\/jem.20090222","volume":"206","author":"JD Brien","year":"2009","unstructured":"Brien, J. D., Uhrlaub, J. L., Hirsch, A., Wiley, C. A. & Nikolich-Zugich, J. Key role of T cell defects in age-related vulnerability to West Nile virus. J. Exp. Med. 206, 2735\u20132745 (2009).","journal-title":"J. Exp. Med."},{"key":"25645_CR9","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1002\/cyto.a.22625","volume":"87","author":"S Van Gassen","year":"2015","unstructured":"Van Gassen, S. et al. FlowSOM: Using self-organizing maps for visualization and interpretation of cytometry data. Cytom. Part A 87, 636\u2013645 (2015).","journal-title":"Cytom. Part A"},{"key":"25645_CR10","doi-asserted-by":"publisher","first-page":"1947LP","DOI":"10.1126\/science.272.5270.1947","volume":"272","author":"DF Tough","year":"1996","unstructured":"Tough, D. F., Borrow, P. & Sprent, J. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272, 1947LP\u20131950LP (1996).","journal-title":"Science"},{"key":"25645_CR11","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.coi.2006.03.010","volume":"18","author":"RE Berg","year":"2006","unstructured":"Berg, R. E. & Forman, J. The role of CD8 T cells in innate immunity and in antigen non-specific protection. Curr. Opin. Immunol. 18, 338\u2013343 (2006).","journal-title":"Curr. Opin. Immunol."},{"key":"25645_CR12","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1073\/pnas.1017340108","volume":"108","author":"K Adachi","year":"2011","unstructured":"Adachi, K. & Davisa, M. M. T-cell receptor ligation induces distinct signaling pathways in na\u00efve vs. antigen-experienced T cells. Proc. Natl Acad. Sci. USA 108, 1549\u20131554 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"25645_CR13","doi-asserted-by":"publisher","unstructured":"Smith-Garvin, J. T cell activation. Annu. Rev. 1\u20139, https:\/\/doi.org\/10.1146\/annurev.immunol.021908.132706 (2009).","DOI":"10.1146\/annurev.immunol.021908.132706"},{"key":"25645_CR14","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.immuni.2015.02.009","volume":"42","author":"HD Hickman","year":"2015","unstructured":"Hickman, H. D. et al. CXCR3 chemokine receptor enables local CD8+ T cell migration for the destruction of virus-infected cells. Immunity 42, 524\u2013537 (2015).","journal-title":"Immunity"},{"key":"25645_CR15","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1002\/stem.5530120502","volume":"12","author":"SF Ziegler","year":"1994","unstructured":"Ziegler, S. F., Ramsdell, F. & Alderson, M. R. The activation antigen CD69. Stem Cells 12, 456\u2013465 (1994).","journal-title":"Stem Cells"},{"key":"25645_CR16","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1093\/gerona\/glx102","volume":"73","author":"JS Davies","year":"2018","unstructured":"Davies, J. S., Thompson, H. L., Pulko, V., Torres, J. P. & Nikolich-\u017dugich, J. Role of cell-intrinsic and environmental age-related changes in altered maintenance of murine T cells in lymphoid organs. J. Gerontol. 73, 1018\u20131026 (2018).","journal-title":"J. Gerontol."},{"key":"25645_CR17","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.bbi.2015.04.009","volume":"48","author":"C Murray","year":"2015","unstructured":"Murray, C. et al. Interdependent and independent roles of type I interferons and IL-6 in innate immune, neuroinflammatory and sickness behaviour responses to systemic poly I: C. Brain. Behav. Immun. 48, 274\u2013286 (2015).","journal-title":"Brain. Behav. Immun."},{"key":"25645_CR18","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1002\/eji.200838959","volume":"39","author":"JK Whitmire","year":"2009","unstructured":"Whitmire, J. K., Eam, B. & Whitton, J. L. Mice deficient in stem cell antigen-1 (Sca1, Ly-6A\/E) develop normal primary and memory CD4+ and CD8+ T-cell responses to virus infection. Eur. J. Immunol. 39, 1494\u20131504 (2009).","journal-title":"Eur. J. Immunol."},{"key":"25645_CR19","doi-asserted-by":"publisher","first-page":"2301","DOI":"10.1084\/jem.188.12.2301","volume":"188","author":"HS Azzam","year":"1998","unstructured":"Azzam, H. S. et al. CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity. J Exp Med. 188, 2301\u20132311 (1998).","journal-title":"J Exp Med"},{"key":"25645_CR20","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1038\/ni1268","volume":"6","author":"AM Intlekofer","year":"2005","unstructured":"Intlekofer, A. M. et al. Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat. Immunol. 6, 1236\u20131244 (2005).","journal-title":"Nat. Immunol."},{"key":"25645_CR21","doi-asserted-by":"publisher","first-page":"4988","DOI":"10.4049\/jimmunol.1002042","volume":"185","author":"A Banerjee","year":"2010","unstructured":"Banerjee, A. et al. Cutting edge: The transcription factor eomesodermin enables CD8+ T cells to compete for the memory cell niche. J. Immunol. 185, 4988\u20134992 (2010).","journal-title":"J. Immunol."},{"key":"25645_CR22","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1038\/80868","volume":"1","author":"KS Schluns","year":"2000","unstructured":"Schluns, K. S., Kieper, W. C., Jameson, S. C. & Lefran\u00e7ois, L. Interleukin-7 mediates the homeostasis of na\u00efve and memory CD8 T cells in vivo. Nat. Immunol. 1, 426\u2013432 (2000).","journal-title":"Nat. Immunol."},{"key":"25645_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8089","volume":"6","author":"V Martinet","year":"2015","unstructured":"Martinet, V. et al. Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8+ T cells. Nat. Commun. 6, 7089 (2015).","journal-title":"Nat. Commun."},{"key":"25645_CR24","doi-asserted-by":"publisher","unstructured":"Delong, J. H. et al. Cytokine- and TCR-mediated regulation of T cell expression of Ly6C and Sca-1. https:\/\/doi.org\/10.4049\/jimmunol.1701154 (2019).","DOI":"10.4049\/jimmunol.1701154"},{"key":"25645_CR25","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1084\/jem.20040712","volume":"200","author":"RMO Connell","year":"2004","unstructured":"Connell, R. M. O. et al. Type I interferon production enhances susceptibility to listeria monocytogenes infection. J. Exp. Med. 200, 4\u201312 (2004).","journal-title":"J. Exp. Med."},{"key":"25645_CR26","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/ni.3043","volume":"16","author":"RB Fulton","year":"2015","unstructured":"Fulton, R. B. et al. The TCR\u2019s sensitivity to self peptide-MHC dictates the ability of naive CD8(+) T cells to respond to foreign antigens. Nat. Immunol. 16, 107\u2013117 (2015).","journal-title":"Nat. Immunol."},{"key":"25645_CR27","doi-asserted-by":"crossref","unstructured":"Moran, A. E. et al. T cell receptor signal strength in T reg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. J. Exp. Med. 208, 1279\u20131289 (2011).","DOI":"10.1084\/jem.20110308"},{"key":"25645_CR28","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1038\/ni1513","volume":"8","author":"A Link","year":"2007","unstructured":"Link, A. et al. Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells. Nat. Immunol. 8, 1255\u20131265 (2007).","journal-title":"Nat. Immunol."},{"key":"25645_CR29","doi-asserted-by":"publisher","first-page":"13306","DOI":"10.1073\/pnas.96.23.13306","volume":"96","author":"WC Kieper","year":"1999","unstructured":"Kieper, W. C. & Jameson, S. C. Homeostatic expansion and phenotypic conversion of na\u00efve T cells in response to self peptide\/MHC ligands. Proc. Natl Acad. Sci. USA 96, 13306\u201313311 (1999).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"25645_CR30","doi-asserted-by":"publisher","first-page":"8732","DOI":"10.1073\/pnas.161126098","volume":"98","author":"JT Tan","year":"2001","unstructured":"Tan, J. T. et al. IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc. Natl Acad. Sci. USA 98, 8732\u20138737 (2001).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"25645_CR31","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1002\/eji.201040760","volume":"41","author":"A H\u00e4nninen","year":"2011","unstructured":"H\u00e4nninen, A., Maksimow, M., Alam, C., Morgan, D. J. & Jalkanen, S. Ly6C supports preferential homing of central memory CD8+ T cells into lymph nodes. Eur. J. Immunol. 41, 634\u2013644 (2011).","journal-title":"Eur. J. Immunol."},{"key":"25645_CR32","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nature07657","volume":"458","author":"D Zehn","year":"2009","unstructured":"Zehn, D., Lee, S. Y. & Bevan, M. J. Complete but curtailed T-cell response to very low-affinity antigen. Nature 458, 211\u2013214 (2009).","journal-title":"Nature"},{"key":"25645_CR33","doi-asserted-by":"publisher","first-page":"595","DOI":"10.5483\/BMBRep.2012.45.11.210","volume":"45","author":"HK Kong","year":"2012","unstructured":"Kong, H. K. & Park, J. H. Characterization and function of human ly-6\/upar molecules. BMB Rep. 45, 595\u2013603 (2012).","journal-title":"BMB Rep."},{"key":"25645_CR34","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1084\/jem.20050821","volume":"202","author":"GA Kolumam","year":"2005","unstructured":"Kolumam, G. A., Thomas, S., Thompson, L. J., Sprent, J. & Murali-Krishna, K. Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection. J. Exp. Med. 202, 637\u2013650 (2005).","journal-title":"J. Exp. Med."},{"key":"25645_CR35","doi-asserted-by":"publisher","unstructured":"Curtsinger, J. M., Valenzuela, J. O., Agarwal, P., Lins, D. & Mescher, M. F. Cutting Edge: Type I IFNs provide a third signal to CD8. 8\u201313, https:\/\/doi.org\/10.4049\/jimmunol.174.8.4465 (2020).","DOI":"10.4049\/jimmunol.174.8.4465"},{"key":"25645_CR36","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.cytogfr.2010.05.002","volume":"21","author":"F Mattei","year":"2010","unstructured":"Mattei, F., Schiavoni, G. & Tough, D. F. Regulation of immune cell homeostasis by type I interferons. Cytokine Growth Factor Rev. 21, 227\u2013236 (2010).","journal-title":"Cytokine Growth Factor Rev."},{"key":"25645_CR37","doi-asserted-by":"publisher","first-page":"5965","DOI":"10.1128\/JVI.75.13.5965-5976.2001","volume":"75","author":"JM McNally","year":"2001","unstructured":"McNally, J. M. et al. Attrition of bystander CD8 T cells during virus-induced T-cell and interferon responses. J. Virol. 75, 5965\u20135976 (2001).","journal-title":"J. Virol."},{"key":"25645_CR38","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.4049\/jimmunol.1001140","volume":"185","author":"HD Marshall","year":"2010","unstructured":"Marshall, H. D., Prince, A. L., Berg, L. J. & Welsh, R. M. IFN- and self-MHC divert CD8 T cells into a distinct differentiation pathway characterized by rapid acquisition of effector functions. J. Immunol. 185, 1419\u20131428 (2010).","journal-title":"J. Immunol."},{"key":"25645_CR39","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.virol.2016.03.005","volume":"493","author":"SL Urban","year":"2016","unstructured":"Urban, S. L., Berg, L. J. & Welsh, R. M. Type 1 interferon licenses na??ve CD8 T cells to mediate anti-viral cytotoxicity. Virology 493, 52\u201359 (2016).","journal-title":"Virology"},{"key":"25645_CR40","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1016\/j.immuni.2008.11.002","volume":"29","author":"CD Surh","year":"2008","unstructured":"Surh, C. D. & Sprent, J. Homeostasis of naive and memory T cells. Immunity 29, 848\u2013862 (2008).","journal-title":"Immunity"},{"key":"25645_CR41","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1126\/science.272.5258.54","volume":"272","author":"R Ahmed","year":"1996","unstructured":"Ahmed, R. & Gray, D. Immunological memory and protective immunity: understanding their relation. Science 272, 54\u201360 (1996).","journal-title":"Science"},{"key":"25645_CR42","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1111\/j.1474-9726.2012.00867.x","volume":"11","author":"G Li","year":"2012","unstructured":"Li, G., Smithey, M. J., Rudd, B. D. & Nikolich-\u017dugich, J. Age-associated alterations in CD8\u03b1+ dendritic cells impair CD8 T-cell expansion in response to an intracellular bacterium. Aging Cell 11, 968\u2013977 (2012).","journal-title":"Aging Cell"},{"key":"25645_CR43","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/0092-8674(94)90169-4","volume":"76","author":"KA Hogquist","year":"2017","unstructured":"Hogquist, K. A. et al. T cell receptor antagonist peptides induce positive selection. Cell 76, 17\u201327 (2017).","journal-title":"Cell"}],"updated-by":[{"DOI":"10.1038\/s41467-024-44731-3","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000}}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-25645-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-25645-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-25645-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T07:04:06Z","timestamp":1705043046000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-25645-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,6]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["25645"],"URL":"https:\/\/doi.org\/10.1038\/s41467-021-25645-w","relation":{"correction":[{"id-type":"doi","id":"10.1038\/s41467-024-44731-3","asserted-by":"object"}]},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,6]]},"assertion":[{"value":"8 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 January 2024","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41467-024-44731-3","URL":"https:\/\/doi.org\/10.1038\/s41467-024-44731-3","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"J.N.\u017d. is on the scientific advisory board and receives research funding from Young Blood, Inc. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5303"}}