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Citations to this article

B cell–intrinsic TLR7 expression drives severe lupus in TLR9-deficient mice
Haylee A. Cosgrove, … , Jeremy S. Tilstra, Mark J. Shlomchik
Haylee A. Cosgrove, … , Jeremy S. Tilstra, Mark J. Shlomchik
Published August 22, 2023
Citation Information: JCI Insight. 2023;8(16):e172219. https://doi.org/10.1172/jci.insight.172219.
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Research Article Immunology Article has an altmetric score of 12

B cell–intrinsic TLR7 expression drives severe lupus in TLR9-deficient mice

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Abstract

The endosomal Toll-like receptor 7 (TLR7) is a major driver of murine and human systemic lupus erythematosus (SLE). The role of TLR7 in lupus pathogenesis is enhanced when the regulatory role of TLR9 is absent. TLR7 signaling in plasmacytoid DCs (pDC) is generally thought to be a major driver of the IFN response and disease pathology; however, the cell types in which TLR7 acts to mediate disease have not been distinguished. To address this, we selectively deleted TLR7 in either CD11c+ cells or CD19+ cells; using a TLR7-floxed allele, we created on the lupus-prone MRL/lpr background, along with a BM chimera strategy. Unexpectedly, TLR7 deficiency in CD11c+ cells had no impact on disease, while TLR7 deficiency in CD19+ B cells yielded mild suppression of proteinuria and a trend toward reduced glomerular disease. However, in TLR9-deficient MRL/lpr mice with accelerated SLE, B cell–specific TLR7 deficiency greatly improved disease. These results support revision of the mechanism by which TLR7 drives lupus and highlight a cis regulatory interaction between the protective TLR9 and the pathogenic TLR7 within the B cell compartment. They suggest B cell–directed, dual TLR7 antagonism/TLR9 agonism or dual TLR7/9 antagonism as a potential future therapeutic strategy to treat SLE.

Authors

Haylee A. Cosgrove, Sebastien Gingras, Minjung Kim, Sheldon Bastacky, Jeremy S. Tilstra, Mark J. Shlomchik

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Total citations by year

Year: 2025 2024 2023 Total
Citations: 6 10 2 18
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Citations to this article (18)

Title and authors Publication Year
IRF7 controls spontaneous autoimmune germinal center and plasma cell checkpoints
Fike AJ, Bricker KN, Gonzalez MV, Maharjan A, Bui T, Nuon K, Emrich SM, Weber JL, Luckenbill SA, Choi NM, Sauteraud R, Liu DJ, Olsen NJ, Caricchio R, Trebak M, Chodisetti SB, Rahman ZS
bioRxiv 2025
Immunization induces inflammation in the mouse heart during spaceflight
Veliz AL, Hughes L, Carrillo D, Pecaut MJ, Kearns-Jonker M
BMC Genomics 2025
AI discovery of TLR agonist-driven phenotypes reveals unique features of peripheral cells from healthy donors and ART-suppressed people living with HIV
Omange RW, Kim SC, Kolhatkar NS, Plott T, Van Trump W, Zhang K, O\u2019Donnell H, Chen D, Hosny A, Wiest M, Barry Z, Addiego EC, Mengistu M, Odorizzi PM, Cai Y, Jacobson R, Wallin JJ
Frontiers in Immunology 2025
IL-7 in autoimmune diseases: mechanisms and therapeutic potential
Zeng Z, Mao H, Lei Q, He Y
Frontiers in Immunology 2025
IRF7 controls spontaneous autoimmune germinal center and plasma cell checkpoints
Fike AJ, Bricker KN, Gonzalez MV, Maharjan A, Bui T, Nuon K, Emrich SM, Weber JL, Luckenbill SA, Choi NM, Sauteraud R, Liu DJ, Olsen NJ, Caricchio R, Trebak M, Chodisetti SB, Rahman ZS
The Journal of Experimental Medicine 2025
Pathogenesis of Autoimmunity/Systemic Lupus Erythematosus (SLE)
Shiozawa S
Cells 2025
NADPH oxidase in B cells and macrophages is protective in murine lupus
Rachael Gordon, Haylee Cosgrove, Anthony Marinov, Sebastien Gingras, Jeremy Tilstra, Allison Campbell, Sheldon Bastacky, Michael Kashgarian, Andras Perl, Kevin Nickerson, Mark Shlomchik
JCI Insight 2024
MDSC-derived S100A8/9 contributes to lupus pathogenesis by promoting TLR7-mediated activation of macrophages and dendritic cells
Yang Y, Zhang X, Jing L, Xiao Y, Gao Y, Hu Y, Jia S, Zhou G, Xiong H, Dong G
Cellular and Molecular Life Sciences 2024
o-Vanillin binds covalently to MAL/TIRAP Lys-210 but independently inhibits TLR2
Rahaman MH, Thygesen SJ, Maxwell MJ, Kim H, Mudai P, Nanson JD, Jia X, Vajjhala PR, Hedger A, Vetter I, Haselhorst T, Robertson AA, Dymock B, Ve T, Mobli M, Stacey KJ, Kobe B
Journal of Enzyme Inhibition and Medicinal Chemistry 2024
Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis.
Wang P, Yang X, Zhang L, Sha S, Huang J, Peng J, Gu J, Pearson JA, Hu Y, Zhao H, Wong FS, Wang Q, Wen L
Nature Communications 2024
Human and Murine Toll-like Receptor-Driven Disease in Systemic Lupus Erythematosus
von Hofsten S, Fenton KA, Pedersen HL
International journal of molecular sciences 2024
Germinal Center vs Extrafollicular Responses in Systemic Autoimmunity: Who Turns the Blade on Self?
He Y, Vinuesa CG
Advances in immunology 2024
Ro60—Roles in RNA Processing, Inflammation, and Rheumatic Autoimmune Diseases
Mahla RS, Jones EL, Dustin LB
International journal of molecular sciences 2024
Roles of TRIM21/Ro52 in connective tissue disease-associated interstitial lung diseases.
Gong X, He S, Cai P
Frontiers in immunology 2024
Tlr7 drives sex- and tissue-dependent effects in Sjögren’s disease
Punnanitinont A, Biswas S, Kasperek EM, Osinski J, Zhu C, Miecznikowski JC, Romano RA, Kramer JM
Frontiers in Cell and Developmental Biology 2024
The path ahead for understanding TLR-driven systemic autoimmunity
Hamerman JA, Barton GM
Current opinion in immunology 2024
For whom the B(c)ell tolls: CXCL4 AIDs human autoimmunity
Tangye SG
Journal of Experimental Medicine 2023
Heightened TLR7 signaling primes BCR-activated B cells in chronic graft-versus-host disease for effector functions
Bracken SJ, Suthers AN, DiCioccio RA, Su H, Anand S, Poe JC, Jia W, Visentin J, Basher F, Jordan CZ, McManigle WC, Li Z, Hakim FT, Pavletic SZ, Bhuiya NS, Ho VT, Horwitz ME, Chao NJ, Sarantopoulos S
Blood Advances 2023

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