FRI0332 IL-2 RESTORED THE REDUCED ABSOLUTE NUMBER OF TREG CELLS IN THE PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY
Authors: Yuying Liang, Hong-Yan Wen, Yanan Duan, Yang Liu, Zhen Yu, Chong Gao
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Idiopathic inflammatory myositis (IIM) is a group of skeletal muscle non-suppurative inflammatory disease, including polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), DM/PM associated with malignancy and so on. The latest studies suggest that there is an increase of Th17 cells levels and a decrease of regulatory T cells (Tregs) levels in IIM, which lead to the Th17/Treg imbalance. IL-2 promotes the proliferation and differentiation of several subsets of CD4<sup>+</sup>T cells and inhibits Th17 cells. It is provided to Tregs from IL-2-producing cells such as activated CD4<sup>+</sup>CD25<sup>low</sup> T cells, NK and NKT cells. Tregs express IL-2Rαβγ, a high affinity IL-2 receptor complex. Therefore, Tregs may be selectively stimulated by low-dose IL-2 and amplified. <h3>Objectives</h3> To explore the quantitative changes of peripheral Th17 cells and Tregs in IIM before and after receiving treatment with low-dose interleukin-2 (IL-2) and analyze the relationship between peripheral Th17 cells and Tregs and clinical indicators disease activity. <h3>Methods</h3> Total 151 IIM patients were enrolled, and 196 healthy adults were used as normal controls. Of them, 76 cases were treated with low dose IL-2 (5.0*10<sup>5</sup> international units (IU) for 5 days). The absolute number of peripheral T, CD4<sup>+</sup> T, CD8<sup>+</sup> T, Th1, Th2, Th17 and Treg subsets were analyzed by flow cytometry. Laboratory examinations were analyzed retrospectively. Since the data was disregarded from the normal distribution, the median four quantile method was used for statistical description. Multiple samples were compared with Kruskal-Wallis H test, and the correlation between variables was Spearman rank correlation analysis. <h3>Results</h3> (1) In the patients, the absolute number of Treg cells was significantly decreased as compared with that in the control group (P&lt;0.05) and increased by treated with a low dose IL-2. After IL-2 treatment, the absolute numbers of T, CD4<sup>+</sup> T, CD8<sup>+</sup> T, Th1, Th2 and Th17 cells and the ratio of Th17/Treg were still significantly lower than that in the control group (P&lt;0.05); the ratio of Th17/Treg in the patients was not significantly different from that in the control group (P&gt;0.05). (2) The peripheral Th17 cells levels were negatively correlated with ESR, CRP, LDH and HBDH (r=-0.42, r=-0.28, r=-0.21, r=-0.20, P&lt;0.05); the peripheral Treg cells levels were negatively correlated with ESR, CRP, LDH and HBDH (r=-0.18, r=-0.20, r=-0.18, r=-0.20, P&lt;0.05); the ratio of Th17/Treg was negatively correlated with ESR (r=-0.23, P&lt;0.05). <h3>Conclusion</h3> The absolute number of peripheral Th17 cells and Tregs declined significantly in IIM, and had correlation with ESR, CRP, LDH and HBDH. However, after receiving treatment with low-dose IL-2, the Tregs levels elevated, which means that IL-2 may plays an essential role in the differentiation and development of Tregs. It also provides new thought and strategy for the therapy of IIM. <h3>References</h3> [1] Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases [J]. Autoimmunity reviews, 2014, 13(6): 668-677. [2] Bluestone J A, Trotta E, Xu D. The therapeutic potential of regulatory T cells for the treatment of autoimmune disease[J]. Expert opinion on therapeutic targets, 2015, 19(8): 1091-1103. [3] Peterson, L. B., Bell, C. J. M., Howlett, S. K. A long-lived IL-2 mutein that selectively activates and expands regulatory T cells as a therapy for autoimmune disease[J]. Journal of Autoimmunity, 2018, 95: 1-14. [4] Fan, M. Y., Low, J. S., Tanimine, N. Differential Roles of IL-2 Signaling in Developing versus Mature Tregs[J]. Cell Reports, 2018, 25(5): 1204-1213. <h3>Disclosure of Interests</h3> None declared