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The Role of IL-23/IL-17 Axis in Lupus Nephritis¹

Division of Rheumatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215

T cells that express IL-17 infiltrate the kidneys of patients with systemic lupus erythematosus. A significant proportion of these cells are CD3⁺CD4^–CD8^– double-negative T cells. In this study, we show that double-negative T cells from MRL/lpr mice express high amounts of IL-17 and that as disease progressively worsens, the expression of IL-17 and of IL-23 receptor in lymphocytes from these mice increases. Lymph node cells from lupus-prone mice, but not control mice, treated in vitro with IL-23 induce nephritis when transferred to non-autoimmune, lymphocyte-deficient Rag-1^–/– mice. Kidney specimens from these recipient mice show significant Ig and complement deposition. The data indicate that an aberrantly active IL-23/IL-17 axis contributes to the development of nephritis in lupus-prone mice.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work is supported by National Institute of Health Grants R01 AI42269, R01 AI49954, and 1 K23 AR055672-01A1.

² Z.Z. and V.C.K. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. George C. Tsokos, Beth Israel Deaconess Medical Center, Division of Rheumatology, 330 Brookline Avenue, CLS-937, Boston, MA 02215. E-mail address: gtsokos{at}bidmc.harvard.edu

⁴ Abbreviations used in this paper: SLE, systemic lupus erythematosus; DNT, double-negative T cell; PAS, periodic acid-Schiff; DAPI, 4',6-diamidino-2-phenylindole.