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Comment
. 2023 May;103(5):824-826.
doi: 10.1016/j.kint.2023.01.019.

Resolving a paradox between mouse and man: a genetic link between TLR7 and the pathogenesis of human lupus nephritis

Shaun W Jackson  1 , Brad H Rovin  2
Affiliations
Comment

Resolving a paradox between mouse and man: a genetic link between TLR7 and the pathogenesis of human lupus nephritis

Shaun W Jackson et al. Kidney Int. 2023 May.
No abstract available

Keywords: antinuclear autoantibodies; autoreactive B cells; human genetics; lupus nephritis; toll-like receptors.

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Figures

Figure 1:
Figure 1:. Identification and functional characterization of a pathogenic TLR7 mutation in early-onset SLE.
(A) Using whole genome sequencing, Brown et al. identified a de novo TLR7Y264H missense mutation in a pediatric patient with early onset lupus nephritis. After binding self-antigens derived from apoptotic cells, autoreactive B cells traffic nucleic acid-containing autoantigens to the endosomal receptors TLR7 and TLR9, resulting in dual BCR/TLR-mediated B cell activation. By increasing activation by guanosine-containing self-ligands, TLR7Y264H promotes pathogenic B cell activation and the development of SLE. (B) Parallel extra-follicular and germinal center-dependent B cell activation pathways contribute to the production of autoantibody-producing plasma cells during humoral autoimmunity. Surprisingly, autoantibodies persisted in Tlr7Y264H mice genetically incapable of forming germinal centers, indicating that extra-follicular B cell activation is the predominant pathway leading to autoantibody formation and the development of immune complex-mediated lupus nephritis. Created with BioRender.com.
See this image and copyright information in PMC

Comment on

  • TLR7 gain-of-function genetic variation causes human lupus.
    Brown GJ, Cañete PF, Wang H, Medhavy A, Bones J, Roco JA, He Y, Qin Y, Cappello J, Ellyard JI, Bassett K, Shen Q, Burgio G, Zhang Y, Turnbull C, Meng X, Wu P, Cho E, Miosge LA, Andrews TD, Field MA, Tvorogov D, Lopez AF, Babon JJ, López CA, Gónzalez-Murillo Á, Garulo DC, Pascual V, Levy T, Mallack EJ, Calame DG, Lotze T, Lupski JR, Ding H, Ullah TR, Walters GD, Koina ME, Cook MC, Shen N, de Lucas Collantes C, Corry B, Gantier MP, Athanasopoulos V, Vinuesa CG. Brown GJ, et al. Nature. 2022 May;605(7909):349-356. doi: 10.1038/s41586-022-04642-z. Epub 2022 Apr 27. Nature. 2022. PMID: 35477763 Free PMC article.

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