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The (Orf)ull truth about IRF5 and type I interferons in SLE

Exactly how nucleic acids trigger type I interferon responses via certain Toll-like receptors has been uncertain. Now, a new pathway involving gene products previously linked to systemic lupus erythematosus but not known to interact has been unravelled, which could be of relevance to the female sex bias in this disease.

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Fig. 1: TASL links nucleic acid activation of IRF5 with the type I interferon response.


  1. Odhams, C. A. et al. Interferon inducible X-linked gene CXorf21 may contribute to sexual dimorphism in systemic lupus erythematosus. Nat. Commun. 10, 2164 (2019).

    Article  Google Scholar 

  2. Bentham, J. et al. Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus. Nat. Genet. 47, 1457–1464 (2015).

    Article  CAS  Google Scholar 

  3. Heinz, L. X. et al. TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9. Nature 581, 316–322 (2020).

    Article  CAS  Google Scholar 

  4. Fitzgerald, K. A. & Kagan, J. C. Toll-like receptors and the control of immunity. Cell 180, 1044–1066 (2020).

    Article  CAS  Google Scholar 

  5. Elkon, K. B. Review: cell death, nucleic acids, and immunity: inflammation beyond the grave. Arthritis Rheumatol. 70, 805–816 (2018).

    Article  Google Scholar 

  6. Baccala, R. et al. Essential requirement for IRF8 and SLC15A4 implicates plasmacytoid dendritic cells in the pathogenesis of lupus. Proc. Natl Acad. Sci. USA 110, 2940–2945 (2013).

    Article  CAS  Google Scholar 

  7. Li, D. et al. IRF5 genetic risk variants drive myeloid-specific IRF5 hyperactivation and presymptomatic SLE. JCI insight 5, e124020 (2020).

    Article  Google Scholar 

  8. Harris, V. M. et al. Lysosomal pH is regulated in a sex dependent manner in immune cells expressing CXorf21. Frontiers Immunol. 10, 578 (2019).

    Article  CAS  Google Scholar 

  9. Souyris, M. et al. TLR7 escapes X chromosome inactivation in immune cells. Sci. Immunol. 3, eaap8855 (2018).

    Article  Google Scholar 

  10. Kobayashi, T. et al. The histidine transporter SLC15A4 coordinates mTOR-dependent inflammatory responses and pathogenic antibody production. Immunity 41, 375–388 (2014).

    Article  CAS  Google Scholar 

Download references


The authors thank Jie An and Gillian I. Rice for helpful discussions. The work of the authors is supported by grants from the National Institutes of Health, Lupus Research Alliance and Rheumatology Research Foundation (to K.B.E.) and the Medical Research Foundation and the NIHR Manchester Biomedical Research Centre (to T.B.). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

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Correspondence to Keith B. Elkon or Tracy A. Briggs.

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Elkon, K.B., Briggs, T.A. The (Orf)ull truth about IRF5 and type I interferons in SLE. Nat Rev Rheumatol 16, 543–544 (2020).

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