Cutting edge: IL-23 receptor deficiency prevents the development of lupus nephritis in C57BL/6-lpr/lpr mice.

نویسندگان

  • Vasileios C Kyttaris
  • Zheng Zhang
  • Vijay K Kuchroo
  • Mohamed Oukka
  • George C Tsokos
چکیده

IL-17-producing T cells infiltrate kidneys of patients with lupus nephritis, and IL-23-treated lymph node cells from lupus-prone mice may transfer disease to Rag1-deficient mice. In this study, we show that IL-23R-deficient lupus-prone C57BL/6-lpr/lpr mice display decreased numbers of CD3(+)CD4(-)CD8(-) cells and IL-17A-producing cells in the lymph nodes and produce less anti-DNA Abs. In addition, clinical and pathology measures of lupus nephritis are abrogated. The presented experiments document the importance of IL-23R-mediated signaling in the development of lupus nephritis and urge the consideration of proper biologics for the treatment of the disease.

منابع مشابه

NLRP3 and ASC suppress lupus-like autoimmunity by driving the immunosuppressive effects of TGF-β receptor signalling.

OBJECTIVES The NLRP3/ASC inflammasome drives host defence and autoinflammatory disorders by activating caspase-1 to trigger the secretion of mature interleukin (IL)-1β/IL-18, but its potential role in autoimmunity is speculative. METHODS We generated and phenotyped Nlrp3-deficient, Asc-deficient, Il-1r-deficient and Il-18-deficient C57BL/6-lpr/lpr mice, the latter being a mild model of sponta...

متن کامل

IRF4 deficiency abrogates lupus nephritis despite enhancing systemic cytokine production.

The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved in the pathogenesis of systemic lupus and lupus nephritis, but the contribution of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To determine a putative pathogenic role of IRF4 in lupus, we crossed Irf4-deficient mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated w...

متن کامل

Interleukin-1 receptor-associated kinase-M suppresses systemic lupus erythematosus.

OBJECTIVES Interleukin-1 receptor-associated kinase (IRAK)-M suppresses Toll-like receptor (TLR)-mediated activation of innate immunity during infection. A similar role was hypothesised for IRAK-M in autoimmunity. METHODS Irak-m-deficient mice were crossed with autoimmune C57BL/6-lpr/lpr mice and detailed phenotype analysis was performed. RESULTS Irak-m deficiency converted the mild autoimm...

متن کامل

Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens

The Sigirr gene (also known as Tir8) encodes for an orphan receptor of the Toll-like receptor (TLR)/interleukin 1 receptor family that inhibits TLR-mediated pathogen recognition in dendritic cells. Here, we show that Sigirr also inhibits the activation of dendritic cells and B cells upon exposure to RNA and DNA lupus autoantigens. To evaluate the functional role of Sigirr in the pathogenesis of...

متن کامل

IL-12 Deficiency in MRL-Fas Mice Delays Nephritis and Intrarenal IFN- Expression, and Diminishes Systemic Pathology

Autoimmune disease in MRL-Fas lpr mice is characterized by fatal nephritis, systemic pathology, and autoantibodies, mimicking human lupus. We previously reported that 1) intrarenal IL-12 elicits nephritis by fostering the accumulation of intrarenal IFN-␥-secreting T cells, and 2) MRL-Fas lpr mice deficient in the IFN-␥ receptor were spared from nephritis. Therefore, we hypothesized that elimina...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

متن کامل
عنوان ژورنال:
  • Journal of immunology

دوره 184 9  شماره 

صفحات  -

تاریخ انتشار 2010