AB1118 HUMAN CD141+ DENDRITIC CELLS (DCs) REPRESENT A UNIQUE TOLEROGENIC DC SUBSET THAT INDUCE IMMUNE-TOLERANCE IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS

Background: Tolerogenic dendritic cells (DCs) offer promising prospects as cell-based treatment for autoimmune diseases, including systemic lupus erythematosus (SLE). However, the precise mechanisms accounting for tolerogenic DCs mediated immunoregulation in SLE remain incompletely understood. Objectives: We previously identified tolerogenic CD1c⁺DCs played important roles in mesenchymal stem cells transplantation treatment for SLE. Here we further investigate the immunoregulatory effect of CD141⁺DCs in the pathogenesis of lupus. Methods: A total of 12 SLE patients and 12 age-matched and gender-matched healthy subjects were included in the study. The number and percentage of peripheral blood CD141⁺DCs and their expression of functional costimulatory markers (CD40, CD80, CD83, and CD86) were compared between SLE patients and healthy controls. Moreover, the tolerogenic property of CD141⁺DCs and CD1c⁺DCs were compared by stimulating with LPS or SLE serum. Results: Our research revealed the number of peripheral CD141⁺DCs decreased in lupus, which was negatively correlated with SLE disease activity index score. Moreover, CD141⁺DCs in SLE patients exhibited distinct tolerogenic properties by decreasing expression of CD40, CD80, CD86 compared with healthy controls. Furthermore, CD141⁺DCs exhibited superior tolerogenicity compared to CD1c⁺DCs in SLE, by reducing expression of CD86 and reducing production of TNFα. Conclusion: CD141⁺DCs may play a more significant role than the commonly studied CD1c⁺DCs in ameliorating immune dysfunction and maintaining immune homeostasis in SLE. Our findings contribute to a better understanding of the immunoregulatory mechanisms underlying SLE and pave the way for novel therapeutic approaches targeting CD141⁺DCs. REFERENCES: [1] Yuan X, Qin X, Wang D, et al. Mesenchymal stem cell therapy induces FLT3L and CD1c⁺ dendritic cells in systemic lupus erythematosus patients. Nat Commun. 2019;10(1):2498. [2] Chu CC, Ali N, Karagiannis P, et al. Resident CD141 (BDCA3)⁺ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation. J Exp Med. 2012;209(5):935-945. [3] Comi M, Avancini D, Santoni de Sio F, et al. Coexpression of CD163 and CD141 identifies human circulating IL-10-producing dendritic cells (DC-10). Cell Mol Immunol. 2020;17(1):95-107. [4] Sachamitr P, Leishman AJ, Davies TJ, Fairchild PJ. Directed Differentiation of Human Induced Pluripotent Stem Cells into Dendritic Cells Displaying Tolerogenic Properties and Resembling the CD141⁺ Subset. Front Immunol. 2018;8:1935. [5] Worbs T, Hammerschmidt SI, Förster R. Dendritic cell migration in health and disease. Nat Rev Immunol. 2017;17(1):30-48. [6] Adamik J, Munson PV, Hartmann FJ, et al. Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells. Nat Commun. 2022;13(1):5184. [7] Breton G, Lee J, Zhou YJ, et al. Circulating precursors of human CD1c⁺ and CD141⁺ dendritic cells. J Exp Med. 2015;212(3):401-413. Acknowledgements: NIL. Disclosure of Interests: None declared.