{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:28:25Z","timestamp":1790713705680,"version":"4.1.0"},"reference-count":84,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-21877-8","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T12:12:32Z","timestamp":1761912752000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Immunomodulation of behavior impairment via spleen-specific targeting lipid nanoparticles in a MeCP2 transgenic mouse model"],"prefix":"10.1038","volume":"15","author":[{"given":"Shu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aygun","family":"Teymur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatin","family":"Atrooz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheereen","family":"Majd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandra","family":"Mohan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samina","family":"Salim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianfu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"21877_CR1","doi-asserted-by":"publisher","first-page":"e02676","DOI":"10.7554\/eLife.02676","volume":"3","author":"LD Heckman","year":"2014","unstructured":"Heckman, L. D., Chahrour, M. H. & Zoghbi, H. Y. Rett-causing mutations reveal two domains critical for MeCP2 function and for toxicity in MECP2 duplication syndrome mice. Elife 3, e02676 (2014).","journal-title":"Elife"},{"issue":"6","key":"21877_CR2","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/0092-8674(92)90610-O","volume":"69","author":"JD Lewis","year":"1992","unstructured":"Lewis, J. D. et al. Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 69 (6), 905\u2013914 (1992).","journal-title":"Cell"},{"issue":"2","key":"21877_CR3","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/13810","volume":"23","author":"RE Amir","year":"1999","unstructured":"Amir, R. E. et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23 (2), 185\u2013188 (1999).","journal-title":"Nat. Genet."},{"issue":"4","key":"21877_CR4","doi-asserted-by":"publisher","first-page":"e2119078119","DOI":"10.1073\/pnas.2119078119","volume":"119","author":"J Zhou","year":"2022","unstructured":"Zhou, J. et al. Disruption of MeCP2\u2013TCF20 complex underlies distinct neurodevelopmental disorders. Proc. Natl. Acad. Sci. 119(4), e2119078119 (2022).","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"6039","key":"21877_CR5","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1126\/science.1206593","volume":"333","author":"CM McGraw","year":"2011","unstructured":"McGraw, C. M., Samaco, R. C. & Zoghbi, H. Y. Adult neural function requires MeCP2. Science 333 (6039), 186\u2013186 (2011).","journal-title":"Science"},{"issue":"583","key":"21877_CR6","doi-asserted-by":"publisher","first-page":"eaaz7785","DOI":"10.1126\/scitranslmed.aaz7785","volume":"13","author":"Y Shao","year":"2021","unstructured":"Shao, Y. et al. Antisense oligonucleotide therapy in a humanized mouse model of MECP2 duplication syndrome. Sci. Transl. Med. 13 (583), eaaz7785 (2021).","journal-title":"Sci. Transl. Med."},{"issue":"7580","key":"21877_CR7","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/nature16159","volume":"528","author":"Y Sztainberg","year":"2015","unstructured":"Sztainberg, Y. et al. Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides. Nature 528 (7580), 123\u2013126 (2015).","journal-title":"Nature"},{"key":"21877_CR8","doi-asserted-by":"crossref","unstructured":"Hariharan, V. N. et al. Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality for one year in an MECP2 duplication mouse model. bioRxiv (2025).","DOI":"10.1101\/2025.03.26.645328"},{"issue":"1","key":"21877_CR9","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/s41593-024-01838-6","volume":"28","author":"D Yang","year":"2025","unstructured":"Yang, D. et al. An RNA editing strategy rescues gene duplication in a mouse model of MECP2 duplication syndrome and nonhuman primates. Nat. Neurosci. 28 (1), 72\u201383 (2025).","journal-title":"Nat. Neurosci."},{"key":"21877_CR10","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.jaut.2012.12.012","volume":"41","author":"KA Koelsch","year":"2013","unstructured":"Koelsch, K. A. et al. Functional characterization of the MECP2\/IRAK1 lupus risk haplotype in human T cells and a human MECP2 Transgenic mouse. J. Autoimmun. 41, 168\u2013174 (2013).","journal-title":"J. Autoimmun."},{"key":"21877_CR11","first-page":"870","volume-title":"Overexpression of methyl-CpG-binding protein 2 and autoimmunity: evidence from MECP2 duplication syndrome, lupus, MECP2 transgenic and Mecp2 deficient mice","author":"AH Sawalha","year":"2013","unstructured":"Sawalha, A. H. Overexpression of methyl-CpG-binding protein 2 and autoimmunity: evidence from MECP2 duplication syndrome, lupus, MECP2 transgenic and Mecp2 deficient mice Vol. 22, 870\u2013872 (Sage Publications, 2013)."},{"key":"21877_CR12","unstructured":"Kaufman, K. M. et al. Fine mapping of Xq28: both MECP2 and IRAK1 contribute to risk for systemic lupus erythematosus in multiple Ancxestral groups. Ann. Rheum. Dis. 2012, annrheumdis (2012-201851)."},{"issue":"3","key":"21877_CR13","doi-asserted-by":"publisher","first-page":"e1727","DOI":"10.1371\/journal.pone.0001727","volume":"3","author":"AH Sawalha","year":"2008","unstructured":"Sawalha, A. H. et al. Common variants within MECP2 confer risk of systemic lupus erythematosus. PloS One. 3 (3), e1727 (2008).","journal-title":"PloS One"},{"issue":"4","key":"21877_CR14","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1002\/art.24360","volume":"60","author":"R Webb","year":"2009","unstructured":"Webb, R. et al. Variants within MECP2, a key transcription regulator, are associated with increased susceptibility to lupus and differential gene expression in patients with systemic lupus erythematosus. Arthritis Rheumatism: Official J. Am. Coll. Rheumatol. 60 (4), 1076\u20131084 (2009).","journal-title":"Arthritis Rheumatism: Official J. Am. Coll. Rheumatol."},{"issue":"21","key":"21877_CR15","doi-asserted-by":"publisher","first-page":"2679","DOI":"10.1093\/hmg\/ddh282","volume":"13","author":"AL Collins","year":"2004","unstructured":"Collins, A. L. et al. Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum. Mol. Genet. 13 (21), 2679\u20132689 (2004).","journal-title":"Hum. Mol. Genet."},{"issue":"163","key":"21877_CR16","doi-asserted-by":"publisher","first-page":"163ra158","DOI":"10.1126\/scitranslmed.3004430","volume":"4","author":"T Yang","year":"2012","unstructured":"Yang, T. et al. Overexpression of methyl-CpG binding protein 2 impairs TH1 responses. Sci. Transl. Med. 4 (163), 163ra158\u2013163ra158 (2012).","journal-title":"Sci. Transl. Med."},{"key":"21877_CR17","doi-asserted-by":"publisher","first-page":"1370254","DOI":"10.3389\/fimmu.2024.1370254","volume":"15","author":"Y Li","year":"2024","unstructured":"Li, Y., Zhang, S., Tang, C., Mohan, C. & Wu, T. Autoimmune and neuropsychiatric phenotypes in a Mecp2 Transgenic mouse model on C57BL\/6 background. Front. Immunol. 15, 1370254 (2024).","journal-title":"Front. Immunol."},{"issue":"4","key":"21877_CR18","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/mp.2010.21","volume":"15","author":"N Derecki","year":"2010","unstructured":"Derecki, N., Privman, E. & Kipnis, J. Rett syndrome and other autism spectrum disorders\u2014brain diseases of immune malfunction? Mol. Psychiatry. 15 (4), 355\u2013363 (2010).","journal-title":"Mol. Psychiatry"},{"issue":"4","key":"21877_CR19","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.immuni.2015.03.013","volume":"42","author":"JC Cronk","year":"2015","unstructured":"Cronk, J. C. et al. Methyl-CpG binding protein 2 regulates microglia and macrophage gene expression in response to inflammatory stimuli. Immunity 42 (4), 679\u2013691 (2015).","journal-title":"Immunity"},{"key":"21877_CR20","doi-asserted-by":"publisher","first-page":"113834","DOI":"10.1016\/j.addr.2021.113834","volume":"178","author":"A Gupta","year":"2021","unstructured":"Gupta, A., Andresen, J. L., Manan, R. S. & Langer, R. Nucleic acid delivery for therapeutic applications. Adv. Drug Deliv. Rev. 178, 113834 (2021).","journal-title":"Adv. Drug Deliv. Rev."},{"issue":"1","key":"21877_CR21","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/s43586-022-00104-y","volume":"2","author":"BB Mendes","year":"2022","unstructured":"Mendes, B. B. et al. Nanodelivery of nucleic acids. Nat. Reviews Methods Primers. 2 (1), 24 (2022).","journal-title":"Nat. Reviews Methods Primers"},{"key":"21877_CR22","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.addr.2020.06.002","volume":"154","author":"E Samaridou","year":"2020","unstructured":"Samaridou, E., Heyes, J. & Lutwyche, P. Lipid nanoparticles for nucleic acid delivery: current perspectives. Adv. Drug Deliv. Rev. 154, 37\u201363 (2020).","journal-title":"Adv. Drug Deliv. Rev."},{"issue":"1","key":"21877_CR23","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1021\/acs.accounts.1c00544","volume":"55","author":"Y Eygeris","year":"2021","unstructured":"Eygeris, Y., Gupta, M., Kim, J. & Sahay, G. Chemistry of lipid nanoparticles for RNA delivery. Acc. Chem. Res. 55 (1), 2\u201312 (2021).","journal-title":"Acc. Chem. Res."},{"issue":"2","key":"21877_CR24","doi-asserted-by":"publisher","first-page":"2100109","DOI":"10.1002\/anbr.202100109","volume":"2","author":"L Xu","year":"2022","unstructured":"Xu, L. et al. Lipid nanoparticles for drug delivery. Adv. NanoBiomed Res. 2 (2), 2100109 (2022).","journal-title":"Adv. NanoBiomed Res."},{"issue":"21","key":"21877_CR25","doi-asserted-by":"publisher","first-page":"4001","DOI":"10.1021\/acs.accounts.1c00500","volume":"54","author":"M Qiu","year":"2021","unstructured":"Qiu, M., Li, Y., Bloomer, H. & Xu, Q. Developing biodegradable lipid nanoparticles for intracellular mRNA delivery and genome editing. Acc. Chem. Res. 54 (21), 4001\u20134011 (2021).","journal-title":"Acc. Chem. Res."},{"issue":"12","key":"21877_CR26","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","volume":"6","author":"X Hou","year":"2021","unstructured":"Hou, X., Zaks, T., Langer, R. & Dong, Y. Lipid nanoparticles for mRNA delivery. Nat. Reviews Mater. 6 (12), 1078\u20131094 (2021).","journal-title":"Nat. Reviews Mater."},{"key":"21877_CR27","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.copbio.2021.09.016","volume":"73","author":"E Kon","year":"2022","unstructured":"Kon, E., Elia, U. & Peer, D. Principles for designing an optimal mRNA lipid nanoparticle vaccine. Curr. Opin. Biotechnol. 73, 329\u2013336 (2022).","journal-title":"Curr. Opin. Biotechnol."},{"issue":"6","key":"21877_CR28","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1177\/08971900211009650","volume":"35","author":"SP Teo","year":"2022","unstructured":"Teo, S. P. Review of COVID-19 mRNA vaccines: BNT162b2 and mRNA-1273. J. Pharm. Pract. 35 (6), 947\u2013951 (2022).","journal-title":"J. Pharm. Pract."},{"issue":"5","key":"21877_CR29","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1056\/NEJMoa2035389","volume":"384","author":"LR Baden","year":"2021","unstructured":"Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384 (5), 403\u2013416 (2021).","journal-title":"N. Engl. J. Med."},{"key":"21877_CR30","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s40265-021-01480-7","volume":"81","author":"YN Lamb","year":"2021","unstructured":"Lamb, Y. N. BNT162b2 mRNA COVID-19 vaccine: first approval. Drugs 81, 495\u2013501 (2021).","journal-title":"Drugs"},{"issue":"9","key":"21877_CR31","doi-asserted-by":"publisher","first-page":"2769","DOI":"10.1016\/j.ymthe.2021.05.011","volume":"29","author":"CJ Knudson","year":"2021","unstructured":"Knudson, C. J. et al. Lipid-nanoparticle-encapsulated mRNA vaccines induce protective memory CD8 T cells against a lethal viral infection. Mol. Ther. 29 (9), 2769\u20132781 (2021).","journal-title":"Mol. Ther."},{"issue":"38","key":"21877_CR32","doi-asserted-by":"publisher","first-page":"eadh1655","DOI":"10.1126\/sciadv.adh1655","volume":"9","author":"G Baldeon Vaca","year":"2023","unstructured":"Baldeon Vaca, G. et al. Intranasal mRNA-LNP vaccination protects hamsters from SARS-CoV-2 infection. Sci. Adv. 9 (38), eadh1655 (2023).","journal-title":"Sci. Adv."},{"key":"21877_CR33","doi-asserted-by":"crossref","unstructured":"Zong, Y., Lin, Y., Wei, T. & Cheng, Q. Lipid nanoparticle (LNP) enables mRNA delivery for cancer therapy. Adv. Mater.\u00a02303261. (2023).","DOI":"10.1002\/adma.202303261"},{"key":"21877_CR34","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.omtn.2019.10.045","volume":"19","author":"K Gokita","year":"2020","unstructured":"Gokita, K., Inoue, J., Ishihara, H., Kojima, K. & Inazawa, J. Therapeutic potential of LNP-mediated delivery of miR-634 for cancer therapy. Mol. Therapy-Nucleic Acids. 19, 330\u2013338 (2020).","journal-title":"Mol. Therapy-Nucleic Acids"},{"issue":"11","key":"21877_CR35","doi-asserted-by":"publisher","first-page":"3973","DOI":"10.1021\/acs.molpharmaceut.2c00442","volume":"19","author":"LT Johnson","year":"2022","unstructured":"Johnson, L. T. et al. Lipid nanoparticle (LNP) chemistry can endow unique in vivo RNA delivery fates within the liver that alter therapeutic outcomes in a cancer model. Mol. Pharm. 19 (11), 3973\u20133986 (2022).","journal-title":"Mol. Pharm."},{"issue":"48","key":"21877_CR36","doi-asserted-by":"publisher","first-page":"eadi0508","DOI":"10.1126\/sciadv.adi0508","volume":"9","author":"J Leung","year":"2023","unstructured":"Leung, J. et al. Genetically engineered transfusable platelets using mRNA lipid nanoparticles. Sci. Adv. 9 (48), eadi0508 (2023).","journal-title":"Sci. Adv."},{"issue":"1","key":"21877_CR37","doi-asserted-by":"publisher","first-page":"7101","DOI":"10.1038\/s41467-021-26714-w","volume":"12","author":"E Kenjo","year":"2021","unstructured":"Kenjo, E. et al. Low immunogenicity of LNP allows repeated administrations of CRISPR-Cas9 mRNA into skeletal muscle in mice. Nat. Commun. 12 (1), 7101 (2021).","journal-title":"Nat. Commun."},{"issue":"12","key":"21877_CR38","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1038\/s41565-019-0591-y","volume":"14","author":"A Akinc","year":"2019","unstructured":"Akinc, A. et al. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat. Nanotechnol. 14 (12), 1084\u20131087 (2019).","journal-title":"Nat. Nanotechnol."},{"issue":"44","key":"21877_CR39","doi-asserted-by":"publisher","first-page":"2401445","DOI":"10.1002\/adma.202401445","volume":"36","author":"D Song","year":"2024","unstructured":"Song, D., Zhao, Y., Wang, Z. & Xu, Q. Tuning lipid nanoparticles for RNA delivery to extrahepatic organs. Adv. Mater. 36 (44), 2401445 (2024).","journal-title":"Adv. Mater."},{"issue":"4","key":"21877_CR40","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/s41565-020-0669-6","volume":"15","author":"Q Cheng","year":"2020","unstructured":"Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR\u2013Cas gene editing. Nat. Nanotechnol. 15 (4), 313\u2013320 (2020).","journal-title":"Nat. Nanotechnol."},{"issue":"52","key":"21877_CR41","doi-asserted-by":"publisher","first-page":"e2109256118","DOI":"10.1073\/pnas.2109256118","volume":"118","author":"SA Dilliard","year":"2021","unstructured":"DilliardSA, Cheng, Q. & SiegwartDJ On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles. Proc. Natl. Acad. Sci. 118 (52), e2109256118 (2021).","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"6701","key":"21877_CR42","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1126\/science.adk9428","volume":"384","author":"Y Sun","year":"2024","unstructured":"Sun, Y. et al. In vivo editing of lung stem cells for durable gene correction in mice. Science 384 (6701), 1196\u20131202 (2024).","journal-title":"Science"},{"issue":"1","key":"21877_CR43","doi-asserted-by":"publisher","first-page":"7322","DOI":"10.1038\/s41467-023-42948-2","volume":"14","author":"T Wei","year":"2023","unstructured":"Wei, T. et al. Lung SORT LNPs enable precise homology-directed repair mediated CRISPR\/Cas genome correction in cystic fibrosis models. Nat. Commun. 14 (1), 7322 (2023).","journal-title":"Nat. Commun."},{"issue":"44","key":"21877_CR44","doi-asserted-by":"publisher","first-page":"e202310395","DOI":"10.1002\/anie.202310395","volume":"62","author":"E \u00c1lvarez-Benedicto","year":"2023","unstructured":"\u00c1lvarez-Benedicto, E. et al. Spleen SORT LNP generated in situ CAR T cells extend survival in a mouse model of lymphoreplete B cell lymphoma. Angew. Chem. Int. Ed. 62 (44), e202310395 (2023).","journal-title":"Angew. Chem. Int. Ed."},{"issue":"35","key":"21877_CR45","doi-asserted-by":"publisher","first-page":"2313791","DOI":"10.1002\/adma.202313791","volume":"36","author":"A Vaidya","year":"2024","unstructured":"Vaidya, A. et al. Expanding RNAi to kidneys, lungs, and spleen via selective organ targeting (SORT) SiRNA lipid nanoparticles. Adv. Mater. 36 (35), 2313791 (2024).","journal-title":"Adv. Mater."},{"key":"21877_CR46","doi-asserted-by":"crossref","unstructured":"Iyer, S. et al. Efficient Cas9 nuclease-based editing in skeletal muscle via lipid nanoparticle delivery. bioRxiv 2025:2025.2005. 2012.653518.","DOI":"10.1101\/2025.05.12.653518"},{"issue":"8","key":"21877_CR47","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/nri1669","volume":"5","author":"RE Mebius","year":"2005","unstructured":"Mebius, R. E. & Kraal, G. Structure and function of the spleen. Nat. Rev. Immunol. 5 (8), 606\u2013616 (2005).","journal-title":"Nat. Rev. Immunol."},{"issue":"5","key":"21877_CR48","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1016\/j.immuni.2013.10.010","volume":"39","author":"V Bronte","year":"2013","unstructured":"Bronte, V. & Pittet, M. J. The spleen in local and systemic regulation of immunity. Immunity 39 (5), 806\u2013818 (2013).","journal-title":"Immunity"},{"issue":"5","key":"21877_CR49","first-page":"960","volume":"120","author":"W Ghanima","year":"2012","unstructured":"Ghanima, W., Godeau, B., Cines, D. B. & Bussel, J. B. How I treat immune thrombocytopenia: the choice between splenectomy or a medical therapy as a second-line treatment. Blood J. Am. Soc. Hematol. 120 (5), 960\u2013969 (2012).","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"21877_CR50","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1136\/annrheumdis-2015-eular.6393","volume":"74","author":"G Barron","year":"2015","unstructured":"Barron, G. et al. AB0523 splenectomy in systemic lupus erythematosus versus autoimmune hematological diseases: to late or to early? Ann. Rheum. Dis. 74, 1075 (2015).","journal-title":"Ann. Rheum. Dis."},{"issue":"2","key":"21877_CR51","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1097\/01.sla.0000133182.92780.9c","volume":"240","author":"YN You","year":"2004","unstructured":"You, Y. N., Tefferi, A. & Nagorney, D. M. Outcome of splenectomy for thrombocytopenia associated with systemic lupus erythematosus. Ann. Surg. 240 (2), 286\u2013292 (2004).","journal-title":"Ann. Surg."},{"issue":"23","key":"21877_CR52","first-page":"4782","volume":"121","author":"S Boyle","year":"2013","unstructured":"Boyle, S., White, R. H., Brunson, A. & Wun, T. Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia. Blood J. Am. Soc. Hematol. 121 (23), 4782\u20134790 (2013).","journal-title":"Blood J. Am. Soc. Hematol."},{"issue":"9","key":"21877_CR53","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.2174\/1570159X19666210316092225","volume":"19","author":"D Han","year":"2021","unstructured":"Han, D., Liu, H., Gao, Y. & Feng, J. Targeting brain-spleen crosstalk after stroke: new insights into stroke pathology and treatment. Curr. Neuropharmacol. 19 (9), 1590\u20131605 (2021).","journal-title":"Curr. Neuropharmacol."},{"issue":"5","key":"21877_CR54","first-page":"347","volume":"1","author":"N Dias","year":"2002","unstructured":"Dias, N. & Stein, C. Antisense oligonucleotides: basic concepts and mechanisms. Mol. Cancer Ther. 1 (5), 347\u2013355 (2002).","journal-title":"Mol. Cancer Ther."},{"issue":"1","key":"21877_CR55","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41596-022-00755-x","volume":"18","author":"X Wang","year":"2023","unstructured":"Wang, X. et al. Preparation of selective organ-targeting (SORT) lipid nanoparticles (LNPs) using multiple technical methods for tissue-specific mRNA delivery. Nat. Protoc. 18 (1), 265\u2013291 (2023).","journal-title":"Nat. Protoc."},{"issue":"1","key":"21877_CR56","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1196\/annals.1313.014","volume":"1050","author":"BF Hoyer","year":"2005","unstructured":"Hoyer, B. F., Manz, R. A., Radbruch, A. & Hiepe, F. Long-lived plasma cells and their contribution to autoimmunity. Ann. N. Y. Acad. Sci. 1050 (1), 124\u2013133 (2005).","journal-title":"Ann. N. Y. Acad. Sci."},{"issue":"1","key":"21877_CR57","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/nri702","volume":"2","author":"JJ O\u2019Shea","year":"2002","unstructured":"O\u2019Shea, J. J., Ma, A. & Lipsky, P. Cytokines and autoimmunity. Nat. Rev. Immunol. 2 (1), 37\u201345 (2002).","journal-title":"Nat. Rev. Immunol."},{"issue":"5880","key":"21877_CR58","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1126\/science.1153252","volume":"320","author":"M Chahrour","year":"2008","unstructured":"Chahrour, M. et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320 (5880), 1224\u20131229 (2008).","journal-title":"Science"},{"issue":"1","key":"21877_CR59","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1146\/annurev.biochem.68.1.821","volume":"68","author":"AJ Shaywitz","year":"1999","unstructured":"Shaywitz, A. J. & Greenberg, M. E. CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu. Rev. Biochem. 68 (1), 821\u2013861 (1999).","journal-title":"Annu. Rev. Biochem."},{"issue":"11","key":"21877_CR60","doi-asserted-by":"publisher","first-page":"6413","DOI":"10.4049\/jimmunol.1001829","volume":"185","author":"AY Wen","year":"2010","unstructured":"Wen, A. Y., Sakamoto, K. M. & Miller, L. S. The role of the transcription factor CREB in immune function. J. Immunol. 185 (11), 6413\u20136419 (2010).","journal-title":"J. Immunol."},{"issue":"6560","key":"21877_CR61","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/379081a0","volume":"379","author":"K Barton","year":"1996","unstructured":"Barton, K. et al. Defective thymocyte proliferation and IL-2 production in Transgenic mice expressing a dominant-negative form of CREB. Nature 379 (6560), 81\u201385 (1996).","journal-title":"Nature"},{"issue":"7251","key":"21877_CR62","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/nature08123","volume":"460","author":"N Agarwal","year":"2009","unstructured":"Agarwal, N., Lamichhane, G., Gupta, R., Nolan, S. & Bishai, W. R. Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase. Nature 460 (7251), 98\u2013102 (2009).","journal-title":"Nature"},{"issue":"5","key":"21877_CR63","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1086\/596742","volume":"199","author":"V Pasquinelli","year":"2009","unstructured":"Pasquinelli, V. et al. IFN-\u03b3 production during active tuberculosis is regulated by mechanisms that involve IL-17, SLAM, and CREB. J. Infect. Dis. 199 (5), 661\u2013665 (2009).","journal-title":"J. Infect. Dis."},{"issue":"5","key":"21877_CR64","doi-asserted-by":"publisher","first-page":"2510","DOI":"10.4049\/jimmunol.171.5.2510","volume":"171","author":"S Yano","year":"2003","unstructured":"Yano, S., Ghosh, P., Kusaba, H., Buchholz, M. & Longo, D. L. Effect of promoter methylation on the regulation of IFN-\u03b3 gene during in vitro differentiation of human peripheral blood T cells into a Th2 population. J. Immunol. 171 (5), 2510\u20132516 (2003).","journal-title":"J. Immunol."},{"issue":"3","key":"21877_CR65","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.4049\/jimmunol.173.3.1802","volume":"173","author":"GC Grady","year":"2004","unstructured":"Grady, G. C., Mason, S. M., Stephen, J., Zuniga-Pflucker, J. C. & Michie, A. M. Cyclic adenosine 5\u2032-monophosphate response element binding protein plays a central role in mediating proliferation and differentiation downstream of the pre-TCR complex in developing thymocytes. J. Immunol. 173 (3), 1802\u20131810 (2004).","journal-title":"J. Immunol."},{"issue":"4","key":"21877_CR66","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.immuni.2008.02.015","volume":"28","author":"T Yasuda","year":"2008","unstructured":"Yasuda, T. et al. Erk kinases link pre-B cell receptor signaling to transcriptional events required for early B cell expansion. Immunity 28 (4), 499\u2013508 (2008).","journal-title":"Immunity"},{"issue":"5","key":"21877_CR67","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1158\/0008-5472.CAN-08-3014","volume":"69","author":"J Copp","year":"2009","unstructured":"Copp, J., Manning, G. & Hunter, T. TORC-specific phosphorylation of mammalian target of Rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signaling complex 2. Cancer Res. 69 (5), 1821\u20131827 (2009).","journal-title":"Cancer Res."},{"key":"21877_CR68","doi-asserted-by":"publisher","first-page":"96","DOI":"10.12688\/f1000research.8156.1","volume":"5","author":"S Rangasamy","year":"2016","unstructured":"Rangasamy, S. et al. Reduced neuronal size and mTOR pathway activity in the Mecp2 A140V Rett syndrome mouse model. F1000Research 5, 96 (2016).","journal-title":"F1000Research"},{"issue":"11","key":"21877_CR69","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1016\/j.celrep.2015.08.028","volume":"12","author":"K Tsujimura","year":"2015","unstructured":"Tsujimura, K. et al. miR-199a links MeCP2 with mTOR signaling and its dysregulation leads to Rett syndrome phenotypes. Cell. Rep. 12 (11), 1887\u20131901 (2015).","journal-title":"Cell. Rep."},{"issue":"6","key":"21877_CR70","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1093\/jmcb\/mjy018","volume":"10","author":"W Zhang","year":"2018","unstructured":"Zhang, W. et al. MeCP2 deficiency promotes cell reprogramming by stimulating IGF1\/AKT\/mTOR signaling and activating ribosomal protein-mediated cell cycle gene translation. J. Mol. Cell Biol. 10 (6), 515\u2013526 (2018).","journal-title":"J. Mol. Cell Biol."},{"issue":"1","key":"21877_CR71","doi-asserted-by":"publisher","first-page":"50","DOI":"10.3109\/08830185.2014.933957","volume":"34","author":"Y Liu","year":"2015","unstructured":"Liu, Y. & Zhang, D. Liu X-g: mTOR signaling in T cell immunity and autoimmunity. Int. Rev. Immunol. 34 (1), 50\u201366 (2015).","journal-title":"Int. Rev. Immunol."},{"issue":"12","key":"21877_CR72","doi-asserted-by":"publisher","first-page":"102984","DOI":"10.1016\/j.autrev.2021.102984","volume":"20","author":"C Geier","year":"2021","unstructured":"Geier, C. & Perl, A. Therapeutic mTOR Blockade in systemic autoimmunity: implications for antiviral immunity and extension of lifespan. Autoimmun. rev. 20 (12), 102984 (2021).","journal-title":"Autoimmun. rev."},{"issue":"11","key":"21877_CR73","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1038\/nn.3546","volume":"16","author":"M Costa-Mattioli","year":"2013","unstructured":"Costa-Mattioli, M. & Monteggia, L. M. mTOR complexes in neurodevelopmental and neuropsychiatric disorders. Nat. Neurosci. 16 (11), 1537\u20131543 (2013).","journal-title":"Nat. Neurosci."},{"issue":"1","key":"21877_CR74","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/npp.2011.210","volume":"37","author":"K Sawicka","year":"2012","unstructured":"Sawicka, K. & Zukin, R. S. Dysregulation of mTOR signaling in neuropsychiatric disorders: therapeutic implications. Neuropsychopharmacology 37 (1), 305 (2012).","journal-title":"Neuropsychopharmacology"},{"issue":"2","key":"21877_CR75","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1038\/ni.3076","volume":"16","author":"S Shrestha","year":"2015","unstructured":"Shrestha, S. et al. Treg cells require the phosphatase PTEN to restrain TH1 and TFH cell responses. Nat. Immunol. 16 (2), 178\u2013187 (2015).","journal-title":"Nat. Immunol."},{"issue":"5","key":"21877_CR76","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.4049\/jimmunol.1301005","volume":"191","author":"Z-W Lai","year":"2013","unstructured":"Lai, Z-W. et al. Mechanistic target of Rapamycin activation triggers IL-4 production and necrotic death of double-negative T cells in patients with systemic lupus erythematosus. J. Immunol. 191 (5), 2236\u20132246 (2013).","journal-title":"J. Immunol."},{"issue":"5","key":"21877_CR77","doi-asserted-by":"publisher","first-page":"2234","DOI":"10.1172\/JCI73411","volume":"124","author":"T Koga","year":"2014","unstructured":"Koga, T. et al. CaMK4-dependent activation of AKT\/mTOR and CREM-\u03b1 underlies autoimmunity-associated Th17 imbalance. J. Clin. Investig. 124 (5), 2234\u20132245 (2014).","journal-title":"J. Clin. Investig."},{"issue":"10126","key":"21877_CR78","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1016\/S0140-6736(18)30485-9","volume":"391","author":"Z-W Lai","year":"2018","unstructured":"Lai, Z-W. et al. Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1\/2 trial. Lancet 391 (10126), 1186\u20131196 (2018).","journal-title":"Lancet"},{"issue":"11","key":"21877_CR79","doi-asserted-by":"publisher","first-page":"4250","DOI":"10.1172\/JCI86504","volume":"126","author":"DD Jones","year":"2016","unstructured":"Jones, D. D. et al. mTOR has distinct functions in generating versus sustaining humoral immunity. J. Clin. Investig. 126 (11), 4250\u20134261 (2016).","journal-title":"J. Clin. Investig."},{"issue":"5","key":"21877_CR80","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/nri2546","volume":"9","author":"AW Thomson","year":"2009","unstructured":"Thomson, A. W., Turnquist, H. R. & Raimondi, G. Immunoregulatory functions of mTOR Inhibition. Nat. Rev. Immunol. 9 (5), 324\u2013337 (2009).","journal-title":"Nat. Rev. Immunol."},{"issue":"1\u20134","key":"21877_CR81","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1159\/000363255","volume":"127","author":"JC Gigliotti","year":"2014","unstructured":"Gigliotti, J. C. & Okusa, M. D. The spleen: the forgotten organ in acute kidney injury of critical illness. Nephron Clin. Pract. 127 (1\u20134), 153\u2013157 (2014).","journal-title":"Nephron Clin. Pract."},{"key":"21877_CR82","first-page":"564","volume-title":"Seminars in nephrology","author":"W Su","year":"2003","unstructured":"Su, W. & Madaio, M. P. Recent advances in the pathogenesis of lupus nephritis: autoantibodies and B cells. In Seminars in nephrology 564\u2013568 (Elsevier, 2003)."},{"key":"21877_CR83","doi-asserted-by":"crossref","unstructured":"Yung, S. & Chan, T. M. Autoantibodies and resident renal cells in the pathogenesis of lupus nephritis: getting to know the unknown. J. Immunol. Res. (2012).","DOI":"10.1155\/2012\/139365"},{"key":"21877_CR84","doi-asserted-by":"crossref","unstructured":"Jacob, A. & Alexander, J. J. Complement and blood\u2013brain barrier integrity. Mol. Immunol. 61(2), 149\u2013152 (2014).","DOI":"10.1016\/j.molimm.2014.06.039"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-21877-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-21877-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-21877-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T13:02:53Z","timestamp":1761915773000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-21877-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":84,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["21877"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-21877-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,31]]},"assertion":[{"value":"29 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"38135"}}