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LUPUS NEPHRITIS

A CD4+ T cell population provides B cell help in systemic lupus erythematosus

Nature Reviews Nephrology volume 15, page 123 (2019)Cite this article

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Systemic lupus erythematosus (SLE) is characterized by the development of autoantibodies against double stranded DNA. Virginia Pascual and colleagues previously demonstrated that neutrophils from patients with SLE release an oxidized form of mitochondrial DNA, which induces the production of high levels of type 1 interferons by plasmacytoid dendritic cells (pDCs). They now show that pDCs activated by oxidized mitochondrial DNA induce the production of a CD4+ memory T cell population — which they term T helper 10 (TH10) cells — that provides B cell help through the production of IL-10 and succinate. Moreover, the researchers show that T cells with these characteristics are expanded in the blood of patients with SLE and are present in the tubulointerstitium of patients with proliferative lupus nephritis, suggesting that these cells could be a novel therapeutic target.

To determine the clinical relevance of their in vitro findings, the researchers then assessed whether phenotypically similar cells were present in the blood of patients with SLE. “We found that CXCR5−CXCR3+PD1hiCD4+ T cells, which are distinct from follicular helper T cells but displayed similar phenotypic, functional and metabolic characteristics to TH10 cells, were expanded in the blood of patients with SLE,” notes Pascual. Interestingly, blood levels of these T cells were lowest in children with severe proliferative lupus nephritis, leading the researchers to hypothesize that the cells had migrated from blood to the kidneys of these patients. Indeed, they identified these cells in kidney biopsy samples, where they were located in interstitial areas in close proximity to tubular epithelial cells and B cells. “Although we speculate that these T cells might provide local B cell help in the kidney, it is also important to remember that proximal tubular epithelial cells express the highest density of the succinate receptor, SUCNR1, and that this metabolite has been implicated in the pathogenesis of renovascular hypertension through its capacity to activate the renin–angiotensin system,” says Pascual. “Whether T cell-derived succinate directly contributes to kidney damage in patients with proliferative lupus nephritis — the main class of lupus nephritis that is associated with renovascular hypertension — deserves further study.”

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Further reading

  • Caielli, S. et al. Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus. J. Exp. Med. 213, 697–713 (2016)

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  1. Nature Reviews Nephrology http://www.nature.com/nrneph

    Susan J. Allison

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  1. Susan J. Allison
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Correspondence to Susan J. Allison.

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Allison, S.J. A CD4+ T cell population provides B cell help in systemic lupus erythematosus. Nat Rev Nephrol 15, 123 (2019). https://doi.org/10.1038/s41581-018-0096-1

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