Quaternary Ammonium Compound Disinfectants Reduce Lupus-Associated Splenomegaly by Targeting Neutrophil Migration and T-Cell Fate

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dc.contributor.authorAbdelhamid, Leilaen
dc.contributor.authorCabana-Puig, Xavieren
dc.contributor.authorMu, Qinghuien
dc.contributor.authorMoarefian, Maryamen
dc.contributor.authorSwartwout, Brianna K.en
dc.contributor.authorEden, Kristinen
dc.contributor.authorDas, Prernaen
dc.contributor.authorSeguin, Ryan P.en
dc.contributor.authorXu, Libinen
dc.contributor.authorLowen, Sarahen
dc.contributor.authorLavani, Mitalen
dc.contributor.authorHrubec, Terry C.en
dc.contributor.authorJones, Caroline N.en
dc.contributor.authorLuo, Xin M.en
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.contributor.departmentMechanical Engineeringen
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2021-01-28T14:22:33Zen
dc.date.available2021-01-28T14:22:33Zen
dc.date.issued2020-10-21en
dc.description.abstractHypersensitivity reactions and immune dysregulation have been reported with the use of quaternary ammonium compound disinfectants (QACs). We hypothesized that QAC exposure would exacerbate autoimmunity associated with systemic lupus erythematosus (lupus). Surprisingly, however, we found that compared to QAC-free mice, ambient exposure of lupus-prone mice to QACs led to smaller spleens with no change in circulating autoantibodies or the severity of glomerulonephritis. This suggests that QACs may have immunosuppressive effects on lupus. Using a microfluidic device, we showed that ambient exposure to QACs reduced directional migration of bone marrow-derived neutrophils toward an inflammatory chemoattractant ex vivo. Consistent with this, we found decreased infiltration of neutrophils into the spleen. While bone marrow-derived neutrophils appeared to exhibit a pro-inflammatory profile, upregulated expression of PD-L1 was observed on neutrophils that infiltrated the spleen, which in turn interacted with PD-1 on T cells and modulated their fate. Specifically, QAC exposure hindered activation of splenic T cells and increased apoptosis of effector T-cell populations. Collectively, these results suggest that ambient QAC exposure decreases lupus-associated splenomegaly likely through neutrophil-mediated toning of T-cell activation and/or apoptosis. However, our findings also indicate that even ambient exposure could alter immune cell phenotypes, functions, and their fate. Further investigations on how QACs affect immunity under steady-state conditions are warranted.en
dc.description.notesFunding was received from National Institute of Arthritis and Musculoskeletal and Skin Diseases. We also would like to acknowledge the following funding sources. Environmental Pathology and Toxicology Training Grant funded by the National Institute of Environmental Health Sciences (T32-ES007032) for supporting RP. Seguin. The National Institute of General Medical Sciences of the National Institutes of Health under award number R35GM133610 for supporting M Moarefian.en
dc.description.sponsorshipNational Institute of Arthritis and Musculoskeletal and Skin DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); National Institute of Environmental Health SciencesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS) [T32-ES007032]; National Institute of General Medical Sciences of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R35GM133610]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fimmu.2020.575179en
dc.identifier.issn1664-3224en
dc.identifier.other575179en
dc.identifier.pmid33193366en
dc.identifier.urihttp://hdl.handle.net/10919/102116en
dc.identifier.volume11en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectlupus (SLE)en
dc.subjectneutrophilen
dc.subjectquaternary ammonium compound (QAC)en
dc.subjectautoimmunityen
dc.subjectsplenomegalyen
dc.subjectT cellsen
dc.titleQuaternary Ammonium Compound Disinfectants Reduce Lupus-Associated Splenomegaly by Targeting Neutrophil Migration and T-Cell Fateen
dc.title.serialFrontiers in Immunologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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