Expression of SLAMF6 and Its Functional Significance in Podocytes of Lupus Nephritis

Takashi Igawa¹, Kunihiro Ichinose¹, Masataka Umeda¹, Tomohiro Koga¹, Mizuna Eguchi², Momoko Okamoto², Yushiro Endo², Sousuke Tsuji², Ayuko Takatani¹, Toshimasa Shimizu¹, Shoichi Fukui¹, Remi Sumiyoshi², Shinya Kawashiri², Naoki Iwamoto¹, Mami Tamai¹, Hideki Nakamura¹, Tomoki Origuchi³, George C Tsokos⁴ and Atsushi Kawakami¹, ¹Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ²Department of Immunology and Rheumatology, Unit of Advanced Preventive Medical Sciences, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ³Department of Rehabilitation Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ⁴Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Lupus nephritis

Session Information

Date: Sunday, October 21, 2018

Title: Systemic Lupus Erythematosus – Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Systemic lupus erythematosus(SLE) is multisystem disorder that is caused by tissue damage resulting from antibody and complement-fixing immune complex deposition. Lupus nephritis(LN) is frequent complication and one of the most serious manifestations of SLE. The alteration of the structural protein in podocytes is known as a mechanism of proteinuria in LN. The signaling lymphocyte activation molecule family(the SLAM family) of typeⅠtransmembrane receptors consists of nine related members of the immunoglobulin superfamily and has been reported to mediate important regulatory signals between immune cells through their homophilic and heterophilic interactions(Nat Rev Immunol. 2003 Oct;3(10):813-21).The 1q23 region on human chromosome 1 including the SLAMF cluster of genes, containing SLAMF6 has been identified as a lupus susceptibility locus(Nat Rev Rheumatol. 2010 Jun;6(6):348-57).It has been shown that the expression of signaling lymphocyte activation molecule family 6(SLAMF6) is enhanced in CD4+T cells of SLE patients and is involved in IL-17 production(J Immunol 2012; 188:1206-1212). We sought to examine the functional role of SLAMF6 in lupus podocytes.

Methods: We evaluated the co-expression of nephrin, a podocyte marker and SLAMF6 in kidney of normal controls and LN patients, also in B6 and MRL/lpr mice at the age of 8wk and 16wk by immunofluorescence analysis. We also examined nephrin positive SLAMF6 expression in isolated podocytes from B6 and MRL/lpr kidneys. Then, we analyzed the expression of SLAMF6 in CD4+T cells of isolated kidney and spleen in B6 and MRL/lpr mice. We treated human podocytes with IgG from healthy individuals and LN patients for 24 h and 48h and analyzed the expression of SLAMF6 by real-time PCR.

Results: In the histopathology, the expression of SLAMF6 was increased in nephrin positive area in LN patients and MRL/lpr mice compared to control. Although the expression of nephrin in MRL/lpr mice kidney at 16 wk old decreased compared to B6 mice at same age, the expression of SLAMF6 in podocytes increased in diseased MRL/lpr mice compared to B6 mice. Similarly, the expression of SLAMF6 in CD4+ T cells increased in diseased MRL/lpr mice kidney and spleen compared to B6 mice. The level of SLAMF6 mRNA elevated in human podocytes exposed to LN-derived IgG.

Conclusion: The expression of SLAMF6 is enhanced in LN podocytes, suggesting that the possibility of cooperating with CD4+T cells contributing to its dysfunction. Further examination is needed to nvestigate in detail how SLAMF6 is involved in the development of LN in the future.

Disclosure: T. Igawa, None; K. Ichinose, None; M. Umeda, None; T. Koga, None; M. Eguchi, None; M. Okamoto, None; Y. Endo, None; S. Tsuji, None; A. Takatani, None; T. Shimizu, None; S. Fukui, None; R. Sumiyoshi, None; S. Kawashiri, None; N. Iwamoto, None; M. Tamai, None; H. Nakamura, None; T. Origuchi, None; G. C. Tsokos, None; A. Kawakami, None.

To cite this abstract in AMA style:

Igawa T, Ichinose K, Umeda M, Koga T, Eguchi M, Okamoto M, Endo Y, Tsuji S, Takatani A, Shimizu T, Fukui S, Sumiyoshi R, Kawashiri S, Iwamoto N, Tamai M, Nakamura H, Origuchi T, Tsokos GC, Kawakami A. Expression of SLAMF6 and Its Functional Significance in Podocytes of Lupus Nephritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/expression-of-slamf6-and-its-functional-significance-in-podocytes-of-lupus-nephritis/. Accessed .

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