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Lei Deng,1,2 Xiaoli Pan,1 Yulong Zhang,1 Sujing Sun,1 Liping Lv,1 Lei Gao,1 Ping Ma,1 Huisheng Ai,2 Qianqian Zhou,1 Xiaohui Wang,1 Linsheng Zhan1 1Department of Emerging Transfusion Technology, Institute of Health Service and Transfusion Medicine, Academy of Military Medical Sciences, Beijing, People's Republic of China; 2Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People's Republic of ChinaCorrespondence: Xiaohui Wang; Linsheng ZhanDepartment of Emerging Transfusion Technology, Institute of Health Service and Transfusion Medicine, Academy of Military Medical Sciences, Beijing, People's Republic of ChinaEmail lszhan91@yahoo.com; lovechina1980@163.comBackground: Due to their extraordinary physical and chemical properties, MoS2 nanosheets (MSNs) are becoming more widely used in nanomedicine. However, their influence on immune systems remains unclear.Materials and Methods: Two few-layered MSNs at sizes of 100– 250 nm (S-MSNs) and 400– 500 nm (L-MSNs) were used in this study. Bone marrow-derived dendritic cells (DCs) were exposed to both MSNs at different doses (0, 8, 16, 32, 64, 128 μg/mL) for 48 h and subjected to analyses of surface marker expression, cytokine secretion, lymphoid homing and in vivo T cell priming.Results: Different-sized MSNs of all doses did not affect the viability of DCs. The expression of CD40, CD80, CD86 and CCR7 was significantly higher on both S-MSN- and L-MSN-treated DCs at a dose of 128 μg/mL. As the dose of MSN increased, the secretion of IL-12p70 remained unchanged, the secretion of IL-1β decreased, and the production of TNF-α increased. A significant increase in IL-6 was observed in the 128 μg/mL L-MSN-treated DCs. In particular, MSN treatment dramatically improved the ex vivo movement and in vivo homing ability of both the local resident and blood circulating DCs. Furthermore, the cytoskeleton rearrangement regulated by ROS elevation was responsible for the enhanced homing ability of the MSNs. More robust CD4+ and CD8+ T cell proliferation and activation (characterized by high expression of CD107a, CD69 and ICOS) was observed in mice vaccinated with MSN-treated DCs. Importantly, exposure to MSNs did not interrupt LPS-induced DC activation, homing and T cell priming.Conclusion: Few-layered MSNs ranging from 100 to 500 nm in size could play an immunostimulatory role in enhancing DC maturation, migration and T cell elicitation, making them a good candidate for vaccine adjuvants. Investigation of this study will not only expand the applications of MSNs and other new transition metal dichalcogenides (TMDCs) but also shed light on the in vivo immune-risk evaluation of MSN-based nanomaterials.Keywords: MoS2 nanosheets, dendritic cells, migration, vaccine adjuvant