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EGR2 Deletion Suppresses Anti-DsDNA Autoantibody and IL-17 Production in Autoimmune-Prone B6/lpr Mice: A Differential Immune Regulatory Role of EGR2 in B6/lpr Versus Normal B6 Mice

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dc.contributor.authorDai, Rujuanen
dc.contributor.authorWang, Zhuangen
dc.contributor.authorHeid, Bettinaen
dc.contributor.authorEden, Kristinen
dc.contributor.authorReilly, Christopher M.en
dc.contributor.authorAhmed, S. Ansaren
dc.date.accessioned2022-09-20T16:39:36Zen
dc.date.available2022-09-20T16:39:36Zen
dc.date.issued2022-06-15en
dc.date.updated2022-09-20T15:54:43Zen
dc.description.abstractPrevious studies have reported that deletion of the transcription factor, early growth response protein 2 (EGR2), in normal C57BL/6 (B6) resulted in the development of lupus-like autoimmune disease. However, increased EGR2 expression has been noted in human and murine lupus, which challenges the notion of the autoimmune suppressive role of EGR2 in B6 mice. In this study, we derived both conditional EGR2-/-B6/lpr and EGR2-/-B6 mice to elucidate the immune and autoimmune regulatory roles of EGR2 in autoinflammation (B6/lpr) versus physiologically normal (B6) conditions. We found that conditional EGR2 deletion increased spleen weight, enhanced T cell activation and IFNγ production, and promoted germinal center B cells and LAG3+ regulatory T cells development in both B6/lpr and B6 mice. Nevertheless, EGR2 deletion also showed strikingly differential effects in these two strains on T lymphocyte subsets profile, Foxp3+ Tregs and plasma cell differentiation, anti-dsDNA autoantibodies and immunoglobulins production, and on the induction of IL-17 in in vitro activated splenocytes. Specifically, EGR2 deletion in B6/lpr mice significantly decreased serum levels of anti-dsDNA autoantibodies, total IgG, IgM, IgG1, and IgG2a with reduced plasma cells differentiation. Furthermore, EGR2 deletion in B6/lpr mice had no obvious effect on IgG immunocomplex deposition, medium caliber vessel, and glomeruli inflammation but increased complement C3 immunocomplex deposition and large caliber vessel inflammation in the kidneys. Importantly, we demonstrated that EGR2 deletion in B6/lpr mice significantly reduced pathogenic CD4-CD8-CD3+B220+ double negative T cells, which correlated with the reduced anti-dsDNA autoantibodies in serum and decreased IL-17 production in splenocytes of EGR2-/-B6/lpr mice. Together, our data strongly suggest that the role of EGR2 is complex. The immunoregulatory role of EGR2 varies at normal or autoinflammation conditions and should not be generalized in differential experimental settings.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fimmu.2022.917866en
dc.identifier.eissn1664-3224en
dc.identifier.issn1664-3224en
dc.identifier.pmid35784356en
dc.identifier.urihttp://hdl.handle.net/10919/111932en
dc.identifier.volume13en
dc.language.isoenen
dc.publisherFrontiersen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/35784356en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectEGR2en
dc.subjectIL-17en
dc.subjectanti-dsDNA autoantibodyen
dc.subjectdouble negative T cellen
dc.subjectmurine modelen
dc.subjectplasma cellen
dc.subjectAutoimmune Diseaseen
dc.subjectLupusen
dc.subject2 Aetiologyen
dc.subject2.1 Biological and endogenous factorsen
dc.subjectInflammatory and immune systemen
dc.subject.meshAnimalsen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMiceen
dc.subject.meshInflammationen
dc.subject.meshImmunoglobulin Gen
dc.subject.meshInterleukin-17en
dc.subject.meshAutoantibodiesen
dc.subject.meshAntibodies, Antinuclearen
dc.subject.meshEarly Growth Response Protein 2en
dc.titleEGR2 Deletion Suppresses Anti-DsDNA Autoantibody and IL-17 Production in Autoimmune-Prone B6/lpr Mice: A Differential Immune Regulatory Role of EGR2 in B6/lpr Versus Normal B6 Miceen
dc.title.serialFrontiers in Immunologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournal Articleen
dcterms.dateAccepted2022-05-20en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/VTC Basic Sciences Educationen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/VTC Basic Sciences Education/VTC Basic Sciences Educationen

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