Article Text

Download PDFPDF

AI-17 Response gene to complement-32 expression is upregulated in lupus T cells and promotes IL-17A expression
  1. Anamaria Talpos-Caia1,2,
  2. Alexandru Tatomir2,3,
  3. Vinh Nguyen2,3,
  4. Cornelia D Cudrici4,
  5. Simona Rednic1,
  6. Horea G Rus2,3 and
  7. Violeta Rus2,3
  1. 1University of Medicine and Pharmacy ‘Iuliu Hatieganu’, Cluj-Napoca, Romania
  2. 2University of Maryland School of Medicine, Baltimore, USA
  3. 3Veterans Administration Maryland Health Care System, Baltimore, USA
  4. 4NIAMS, National Institutes of Health, Bethesda, USA


Background RGC (Response Gene to Complement)-32 is a cell cycle regulator widely expressed in normal tissues including brain, kidney, spleen, thymus, multiple tumors and in a variety of cell lines. RGC-32 is localized in the cytoplasm and translocates to the nucleus upon upregulation by complement activation, growth factors and cytokines. RGC-32 is induced by TGFβ in fibroblasts, astrocytes and human renal proximal tubular cells and mediates TGFβ dependent profibrotic pathways. RGC-32 is preferentially upregulated in murine Th17 cells and promotes their differentiation. Patients with Systemic Lupus Erythematosus (SLE) display increased serum levels, expanded frequency of IL-17 producing cells. Whether RGC-32 plays a role in human Th17 differentiation pathway and in Th17 abnormalities in lupus patients has not yet been investigated.

Methods RGC-32 expression in naïve CD4+ T cells from normal controls stimulated with cytokines alone or under Th0, Th1, Th2, Th17 and Treg conditions was determined by flow cytometry and RT-PCR. RGC-32 mRNA expression in PBMCs of lupus patients was assessed with the Autoimmune Disease Profiling cDNA Array spotted with cDNA from CD3+, CD19+ and CD14+ cells and by RT-PCR and flow cytometry. RGC-32 nuclear translocation after stimulation under Th17 conditions was assessed by Western blotting. RGC-32 overexpression and silencing was performed by nucleofection and the effect on IL-17A mRNA levels in CD4+ T cells under Th17 conditions was determined by RT-PCR.

Results RGC-32 mRNA expression was upregulated by TCR stimulation and TGFβ and was more robust under Th17 (3.2±fold) and Treg (2.6±0.8 fold) vs Th1 (1.3±0.4 fold) and Th2 (1.8±0.1 fold) conditions. Moreover, upon stimulation with anti-CD3/CD28 and TGFβ, RGC-32 was translocated into the nucleus. Other cytokines such as IFNα, IL-1β, TNFα did not upregulate RGC-32 mRNA either alone or in combination with TCR stimulation. Overexpression or silencing of RGC-32 in CD4+ T cells upregulated, respectively downregulated IL-17A transcript levels and protein secretion. RGC-32 mRNA and protein level were significantly increased in CD19+ B cells and CD3+ T from lupus patients compared to controls.

Conclusions These results suggest that RGC-32 promotes the differentiation of human Th17 cells. Furthermore, T cells from patients with SLE exhibit increased expression of RGC-32 compared to controls. These data support the idea that RGC-32 signaling may enhance disease expression in SLE by promoting abnormalities in the Th17 pathway and provide a compelling rationale for further investigating the therapeutic potential of blocking RGC-32 in SLE.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.