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Citations to this article

B cell–intrinsic TLR9 expression is protective in murine lupus
Jeremy S. Tilstra, … , Kevin M. Nickerson, Mark J. Shlomchik
Jeremy S. Tilstra, … , Kevin M. Nickerson, Mark J. Shlomchik
Published March 19, 2020
Citation Information: J Clin Invest. 2020;130(6):3172-3187. https://doi.org/10.1172/JCI132328.
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Research Article Autoimmunity Article has an altmetric score of 11

B cell–intrinsic TLR9 expression is protective in murine lupus

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Abstract

Toll-like receptor 9 (TLR9) is a regulator of disease pathogenesis in systemic lupus erythematosus (SLE). Why TLR9 represses disease while TLR7 and MyD88 have the opposite effect remains undefined. To begin to address this question, we created 2 alleles to manipulate TLR9 expression, allowing for either selective deletion or overexpression. We used these to test cell type–specific effects of Tlr9 expression on the regulation of SLE pathogenesis. Notably, Tlr9 deficiency in B cells was sufficient to exacerbate nephritis while extinguishing anti–nucleosome antibodies, whereas Tlr9 deficiency in dendritic cells (DCs), plasmacytoid DCs, and neutrophils had no discernable effect on disease. Thus, B cell–specific Tlr9 deficiency unlinked disease from autoantibody production. Critically, B cell–specific Tlr9 overexpression resulted in ameliorated nephritis, opposite of the effect of deleting Tlr9. Our findings highlight the nonredundant role of B cell–expressed TLR9 in regulating lupus and suggest therapeutic potential in modulating and perhaps even enhancing TLR9 signals in B cells.

Authors

Jeremy S. Tilstra, Shinu John, Rachael A. Gordon, Claire Leibler, Michael Kashgarian, Sheldon Bastacky, Kevin M. Nickerson, Mark J. Shlomchik

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 Total
Citations: 2 10 13 15 5 5 50
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Citations to this article in year 2023 (13)

Title and authors Publication Year
Ezh2 knockout in B cells impairs plasmablast differentiation and ameliorates lupus-like disease in MRL/lpr mice
Xiaoqing Zheng, Mikhail Dozmorov, Colleen Strohlein, Sheldon Bastacky, Amr Sawalha
Arthritis & Rheumatism 2023
Bacterial DNA amplifies neutrophilic inflammation in IL-17-exposed airways
Mues N, Martin RJ, Alam R, Schaunaman N, Dimasuay KG, Kolakowski C, Wright CJ, Zheng L, Chu HW
ERJ Open Research 2023
Toll-like receptors 7 and 9 regulate the proliferation and differentiation of B cells in systemic lupus erythematosus
Wen L, Zhang B, Wu X, Liu R, Fan H, Han L, Zhang Z, Ma X, Chu CQ, Shi X
Frontiers in immunology 2023
Cardiac and vascular complications in lupus: Is there a role for sex?
Corker A, Learmonth M, Patrick DM, DeLeon-Pennell KY, Van Beusecum JP
Frontiers in immunology 2023
Preclinical characterization of the Toll-like receptor 7/8 antagonist MHV370 for lupus therapy
Hawtin S, André C, Collignon-Zipfel G, Appenzeller S, Bannert B, Baumgartner L, Beck D, Betschart C, Boulay T, Brunner HI, Ceci M, Deane J, Feifel R, Ferrero E, Kyburz D, Lafossas F, Loetscher P, Merz-Stoeckle C, Michellys P, Nuesslein-Hildesheim B, Raulf F, Rush JS, Ruzzante G, Stein T, Zaharevitz S, Wieczorek G, Siegel R, Gergely P, Shisha T, Junt T
Cell reports. Medicine 2023
B cell intrinsic TLR7 expression drives severe lupus in TLR9 deficient mice
Haylee Cosgrove, Sebastien Gingras, Minjung Kim, Sheldon Bastacky, Jeremy Tilstra, Mark Jay Shlomchik
JCI Insight 2023
B cell–intrinsic Myd88 regulates disease progression in murine lupus
Tilstra JS, Kim M, Gordon RA, Leibler C, Cosgrove HA, Bastacky S, Nickerson KM, Shlomchik MJ
Journal of Experimental Medicine 2023
For whom the B(c)ell tolls: CXCL4 AIDs human autoimmunity
Tangye SG
Journal of Experimental Medicine 2023
The Role of the Oxidative State and Innate Immunity Mediated by TLR7 and TLR9 in Lupus Nephritis
Echavarria R, Cardona-Muñoz EG, Ortiz-Lazareno P, Andrade-Sierra J, Gómez-Hermosillo LF, Casillas-Moreno J, Campos-Bayardo TI, Román-Rojas D, García-Sánchez A, Miranda-Díaz AG
International journal of molecular sciences 2023
TLR9 ligand sequestration by chemokine CXCL4 negatively affects central B cell tolerance.
Çakan E, Ah Kioon MD, Garcia-Carmona Y, Glauzy S, Oliver D, Yamakawa N, Vega Loza A, Du Y, Schickel JN, Boeckers JM, Yang C, Baldo A, Ivashkiv LB, Young RM, Staudt LM, Moody KL, Nündel K, Marshak-Rothstein A, van der Made CI, Hoischen A, Hayward A, Rossato M, Radstake TRDJ, Cunningham-Rundles C, Ryu C, Herzog EL, Barrat FJ, Meffre E
Journal of Experimental Medicine 2023
Identification of driver genes in lupus nephritis based on comprehensive bioinformatics and machine learning
Wang Z, Hu D, Pei G, Zeng R, Yao Y
Frontiers in immunology 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
Triad3A-Mediated K48-Linked ubiquitination and degradation of TLR9 impairs mitochondrial bioenergetics and exacerbates diabetic cardiomyopathy
Kong C, Guo Z, Liu F, Tang N, Wang M, Yang D, Li C, Yang Z, Ma Y, Wang P, Tang Q
Journal of Advanced Research 2023

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