FRI0276 Aberrant distribution of cd3+cd56+ nkt-like cells in patients with sjÖgren’s syndrome
Authors: H. Chen, L. Zhao, W. Xu, Z. Chen, J. Sun, F. Zhang
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> CD3<sup>+</sup>CD56<sup>+</sup> NKT-like cells are a subset of T cells co-expressing NK cell markers, and bridge innate and adaptive immunity. However, the phenotype and the potential role of NKT-like cells in the pathogenesis of Sjögren's Syndrome (SS) remains elusive. <h3>Objectives</h3> To elucidate the distribution of CD3<sup>+</sup>CD56<sup>+</sup> NKT-like cells in peripheral blood and labial salivary gland (LSG) of SS patients, as well as the immune function of NKT-like cells in SS patients. <h3>Methods</h3> SS patients (n=110) and healthy controls (HC, n=94) were enrolled. Peripheral CD3<sup>+</sup>CD56<sup>+</sup> NKT-like population, proliferation and apoptosis potential, surface chemokine receptors and proinflammatory cytokines secretion were quantified by flow cytometry. The infiltration of NKT-like cells in LSG was examined by immunofluorescence. Serum and tissue levels of CX3CL1 were detected by ELISA and immunohistochemistry, respectively. <i>In vitro</i> transwell migration assay was used to examine the chemotaxis of NKT-like cells induced by chemokines. NKT-like cells were stimulated with CX3CL1 and were quantified the TNF-α and IFN-γ secretion by flow cytometry. <h3>Results</h3> Peripheral CD3<sup>+</sup>CD56<sup>+</sup> NKT-like cells from SS patients were significantly lower than those from HC (3.09%±2.35% vs 5.37±4.06%, p&lt;0.001), which was negatively correlated with ESSDAI (r=−0.523, p=0.009) and serum RF level (r=−0.586, p=0.015). The proliferation rate (35.1%±10.69% vs 36.4±10.75%, p=0.812) or apoptosis rate (13.01%±12.15% vs 12.48±5.28%, p=0.338) of NKT-like cells from SS and HC were comparable. However, NKT-like cells infiltrations into LSG were observed in SS patients but were rarely presented in HC. Serum level of CX3CL1 (936.8±99.82 vs 887.8±82.77 pg/ml, p=0.015) and epithelial CX3CL1 of LSG were higher in SS patients than those in HC. CX3CR1 were expressed on NKT-like cells from both SS and HC (68.25%±22.38% vs 70.06±17.34%, p=0.777). Furthermore, migration assay showed that CX3CR1 promoted NKT-like cells chemotaxis with a dose-dependent manner. Functionally, NKT-like cells from SS patients expressed higher level of CD69 (10.97%±6.75% vs 2.69±1.82%, p&lt;0.0001). Peripheral NKT-like cells from both SS patients and HC secreted high level of TNF-α (70.29%±22.74% vs 81.33±10.76%, p=0.137) and IFN-γ (62.42%±16.66% vs 64.34±14.50%, p=0.759), and low level of IL-4 (4.39%±3.42% vs 2.64±1.90%, p=0.131) and IL-17 (0.30±0.28 vs 0.31±0.30, p=0.967). Importantly, CX3CL1 promoted TNF-α and IFN-γ production by NKT-like cells <i>in vitro</i>. <h3>Conclusions</h3> NKT-like cells were aberrantly depleted in peripheral blood and accumulated in LSG in patients with SS, which was driven by CX3CL1- CX3CR1 axis. NKT-like cells from SS were activated and secreted high level of TNF-α and IFN-γ, which were further promoted by CX3CL1. Thus, NKT-like cells were implicated in the pathogenesis of SS, which might be a potential therapeutic target for SS. <h3>References</h3> [1] Godfrey DI, MacDonald HR, Kronenberg M, et al. Nat Rev Immunol2004;4(3):231–7. [2] Szodoray P, Gal I, Barath S, et al. Scand J Rheumatol2008;37(3):205–12. [3] Yoneda O, Imai T, Nishimura M, et al. Eur J Immunol2003;33(1):53–8. <h3>Disclosure of Interest</h3> None declared