{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:48:53Z","timestamp":1793832533840,"version":"4.6.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"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":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Absent in melanoma 2 (AIM2) has been reported to be a component of inflammasomes in innate immune cells. Surprisingly, AIM2 is expressed by B cells, and higher AIM2 expression is observed in the B cells from lupus patients. To date, the inflammasome-independent function of AIM2 in B cells remains unclear. Here, we report increased expression of AIM2 in human tonsil memory and germinal center (GC) B cells and in memory B cells and plasma cells from the circulation and skin lesions of lupus patients. Conditional knockout of AIM2 in B cells reduces the CD19\n                    <jats:sup>+<\/jats:sup>\n                    B-cell frequency in lymph nodes and spleens, and dampens KLH-induced IgG1-antibody production. In a pristane-induced mouse model of lupus, AIM2 deficiency in B cells attenuates lupus symptoms and reduces the frequency of GC B cells, T follicular helper (Tfh) cells, plasmablast cells, and plasma cells. Furthermore, the loss of AIM2 in human B cells leads to the increased expression of Blimp-1 and reduces the expression of Bcl-6. However, the silencing of Blimp-1 and Bcl-6 has no significant effect on AIM2 expression, indicating that AIM2 might be the upstream regulator for Blimp-1 and Bcl-6. In addition, IL-10 is found to upregulate AIM2 expression via DNA demethylation. Together, our findings reveal that AIM2 is highly expressed in the B cells of lupus patients and promotes B-cell differentiation by modulating the Bcl-6\u2013Blimp-1 axis, providing a novel target for SLE treatment.\n                  <\/jats:p>","DOI":"10.1038\/s41392-021-00725-x","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:02:47Z","timestamp":1631577767000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["AIM2 deficiency in B cells ameliorates systemic lupus erythematosus by regulating Blimp-1\u2013Bcl-6 axis-mediated B-cell differentiation"],"prefix":"10.1038","volume":"6","author":[{"given":"Ming","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longyuan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhidan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianwen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunkai","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianjin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"725_CR1","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/sj.onc.1201206","volume":"15","author":"KL DeYoung","year":"1997","unstructured":"DeYoung, K. 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Science 323, 1057\u20131060 (2009).","journal-title":"Science"},{"key":"725_CR4","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1038\/nature07725","volume":"458","author":"V Hornung","year":"2009","unstructured":"Hornung, V. et al. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458, 514\u2013518 (2009).","journal-title":"Nature"},{"key":"725_CR5","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/nature07710","volume":"458","author":"T Fernandes-Alnemri","year":"2009","unstructured":"Fernandes-Alnemri, T. et al. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458, 509\u2013U505 (2009).","journal-title":"Nature"},{"key":"725_CR6","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/ni.1702","volume":"10","author":"T Burckstummer","year":"2009","unstructured":"Burckstummer, T. et al. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat. Immunol. 10, 266\u2013272 (2009).","journal-title":"Nat. Immunol."},{"key":"725_CR7","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/nm.3908","volume":"21","author":"JE Wilson","year":"2015","unstructured":"Wilson, J. E. et al. Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt. Nat. Med. 21, 906\u2013913 (2015).","journal-title":"Nat. Med."},{"key":"725_CR8","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1056\/NEJMra1100359","volume":"365","author":"GC Tsokos","year":"2011","unstructured":"Tsokos, G. C. Systemic lupus erythematosus. N. Engl. J. Med. 365, 2110\u20132121 (2011).","journal-title":"N. Engl. J. Med."},{"key":"725_CR9","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/cmi.2017.133","volume":"15","author":"H Wu","year":"2018","unstructured":"Wu, H. et al. Epigenetic regulation in B-cell maturation and its dysregulation in autoimmunity. Cell Mol. Immunol. 15, 676\u2013684 (2018).","journal-title":"Cell Mol. Immunol."},{"key":"725_CR10","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1038\/ni.1814","volume":"10","author":"I Dogan","year":"2009","unstructured":"Dogan, I. et al. Multiple layers of B cell memory with different effector functions. Nat. Immunol. 10, 1292\u20131299 (2009).","journal-title":"Nat. Immunol."},{"key":"725_CR11","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1093\/intimm\/dxn005","volume":"20","author":"K Ochiai","year":"2008","unstructured":"Ochiai, K. et al. Regulation of the plasma cell transcription factor Blimp-1 gene by Bach2 and Bcl6. 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AIM2 co-immunization with VP1 is associated with increased memory CD8 T cells and mounts long lasting protection against coxsackievirus B3 challenge. Front. Cell. Infect. Microbiol. 7, 247 (2017).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"725_CR15","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1158\/1535-7163.MCT-18-0832","volume":"18","author":"D Chai","year":"2019","unstructured":"Chai, D. et al. Combining DNA vaccine and AIM2 in H1 nanoparticles exert anti-renal carcinoma effects via enhancing tumor-specific multi-functional CD8(+) T-cell responses. Mol. Cancer Ther. 18, 323\u2013334 (2019).","journal-title":"Mol. Cancer Ther."},{"key":"725_CR16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0183268","volume":"12","author":"A Svensson","year":"2017","unstructured":"Svensson, A. et al. Maturation-dependent expression of AIM2 in human B-cells. 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