THU0083 Cd30 aptamer-slat-shrna chimaeras inhibit th17 differentiation by rorΓt in rheumatoid arthritis
Authors: L. Hui, G.-D. Zhang, B.-B. Cui, H.-H. Tang, L.-J. Xue, Y. Liu, C.-Q. Chu
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> T helper 17 (Th17) cells play a central role in rheumatoid arthritis(RA) via the production of pro-inflammatory cytokines interleukin (IL)−17. SWAP-70- like adapter of T cells (SLAT) has recently emerged as an important regulator of Th17 differentiation. Aptamer-facilitated cell specific delivery of shRNA represents an attractive novel approach for efficient RNAi delivery. However, the role of CD30 aptamer-SLAT-shRNA chimaeras in regulating Th17 differentiation in patients with RA is unclear. <h3>Objectives</h3> SLAT play a crucial role in regulating Th17 cell differentiation and function. This study was undertaken to investigate the role and mechanism of SLAT in Th17 cells differentiation in patients with RA. <h3>Methods</h3> Peripheral blood CD4<sup>+</sup> T cells and synovial fluid CD4<sup>+</sup> T cells derived from RA patients and healthy controls were used to test the effect of SLAT<i> in vitro</i>. CD30 aptamer-SLAT-shRNA chimaeras were generated <i>in vitro</i> and transfected into CD4<sup>+</sup> T cells. The effect of CD30 aptamer-SLAT-shRNA chimaeras on Th17 production and differentiation was detected. <h3>Results</h3> SLAT was expressed mostly in cytoplasm and cell membrane of CD4<sup>+</sup> T cells. The protein levels of SLAT in peripheral blood and synovial fluid CD4<sup>+</sup> T cells of RA patients were higher than that of healthy controls. The effect of CD30 aptamer-SLAT-shRNA chimaeras on Th17 differentiation was due to its ability to sequester SLAT and prevent it from targeting the transcription factor RORγt. <h3>Conclusions</h3> This study reveals new evidence of the role of SLAT in Th17 differentiation in CD4<sup>+</sup> T cells of RA patients. <h3>References</h3> [1] Park H, Li Z, Yang XO, et al. A distinct Lineage of CD4+ T cells regulate tissue inflammation by producing interleukin 17. Nat Immunol2005;6(11):1133–1141. [2] Gupta S, Lee A, Hu C, et al. Molecular cloning of IBP, a SWAP-70 homologous GEF, which is highly expressed in the immune system. Hum Immunol2003;64(4):389–401. [3] Canonigo-Balancio AJ, Fos C, Prod'homme T, et al. SLAT/Def6 plays a critical role in the development of Th17 cell-mediated experimental autoimmune encephalomye- litis. J Immunol2009;183(11):7259–7267. [4] Binder N, Miller C, Yoshida M, et al. Def6 Restrains Osteoclastogenesis and Inflammatory Bone Resorption. J Immunol. 2017;198(9):3436–3447. [5] Wheeler LA, Trifonova R,Vrbanac V, et al. Inhibition of HIV transmission in human cervicovaginal explants and humanized mice using CD4 aptamer-siRNA chimeras. J Clin Invest. 2011;121(6): 2401–2412. [6] Takahashi M, Burnett JC, Rossi JJ. Aptamer-siRNA chimeras for HIV. Adv Exp Med Biol. 2015;848:211–234. [7] Zhang P, Zhao N, Zeng Z, et al. Combination of an aptamer probe to CD4 and antibodies for multicolored cell phenotyping. Am J Clin Pathol2010;134(4): 586–593. [8] Song P, Chou YK, Zhang X, et al. CD4 aptamer-RORgammat shRNA chimera inhibits IL-17 synthesis by human CD4(+) T cells. Biochem Biophys Res Commun2014;452(4):1040–1045. <h3>Acknowledgements</h3> The work was supported by grant 81102274 from the National Natural Science Foundation of China (NSFC) (Hui Lin); grant 10GGYB644SF-023 from the Science and Technology Foundation of Chengdu: (Hui Lin); grant 2017HH0110 from Science and Technology Foundation of International Cooperation of Sichuan Province (Hui Lin) <h3>Disclosure of Interest</h3> None declared