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

• Published in: Annals of the rheumatic diseases Vol. 83; no. Suppl 1; pp. 1890 - 1891
• Main Authors: Yuan, X., Sun, L., Qin, X., Wang, Y., Chen, Y., Liu, S., Wang, D.
• Format: Journal Article
• Language: English
• Published: Kidlington BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2024; Elsevier B.V; Elsevier Limited
• Subjects: Autoimmune diseases; CD11c antigen; CD163 antigen; CD1c antigen; CD3 antigen; CD40 antigen; CD80 antigen; CD83 antigen; CD86 antigen; Cell differentiation; Cell migration; Cell therapy; Cytokines and Chemokines; Dendritic cells; Flow cytometry; FLT3L protein; Homeostasis; Immunological tolerance; Immunoregulation; Innate immunity; Interleukin 10; Lupus; Lymphocytes T; Mesenchymal stem cells; Peripheral blood; Pluripotency; Scientific Abstracts; Stem cell transplantation; Stem cells; Systemic lupus erythematosus; Innate immunity; Cytokines and Chemokines
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2024-eular.3359

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.Figure 1.CD141+DCs decrease in patients with SLE(A)FACS gating strategy used to identify CD141+DCs: Lin(CD3/19/56/14)-HLA-DR+CD11c+CD141+.（B)Flow cytometry analyses of CD141+DCs in PBMCs between SLE patients and healthy controls. (C-D)Quantification of CD141+DCs in (B). (E)The correlation between the percentage of CD141+DCs and SLEDAI score was analyzed by Pearson’s correlation coefficient.Acknowledgements:NIL.Disclosure of Interests:None declared.