The role of IL-23/IL-17 axis in lupus nephritis.
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.
Zhang
Zheng
Z
Division of Rheumatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Kyttaris
Vasileios C
VC
Tsokos
George C
GC
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D053759:Interleukin-23 / Q000502:physiology*; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
D020381:Interleukin-17; D053759:Interleukin-23; D018123:Receptors, Interleukin; C528688:interleukin-23 receptor, mouse