scholarly journals Autologous tolerogenic dendritic cells derived from monocytes of systemic lupus erythematosus patients and healthy donors show a stable and immunosuppressive phenotype

Immunology ◽  
2017 ◽  
Vol 152 (4) ◽  
pp. 648-659 ◽  
Author(s):  
Javiera Obreque ◽  
Fabián Vega ◽  
Andy Torres ◽  
Loreto Cuitino ◽  
Juan P. Mackern-Oberti ◽  
...  
Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1291 ◽  
Author(s):  
Ritprajak ◽  
Kaewraemruaen ◽  
Hirankarn

Tolerogenic dendritic cells (tolDCs) are central players in the initiation and maintenance of immune tolerance and subsequent prevention of autoimmunity. Recent advances in treatment of autoimmune diseases including systemic lupus erythematosus (SLE) have focused on inducing specific tolerance to avoid long-term use of immunosuppressive drugs. Therefore, DC-targeted therapies to either suppress DC immunogenicity or to promote DC tolerogenicity are of high interest. This review describes details of the typical characteristics of in vivo and ex vivo tolDC, which will help to select a protocol that can generate tolDC with high functional quality for clinical treatment of autoimmune disease in individual patients. In addition, we discuss the recent studies uncovering metabolic pathways and their interrelation intertwined with DC tolerogenicity. This review also highlights the clinical implications of tolDC-based therapy for SLE treatment, examines the current clinical therapeutics in patients with SLE, which can generate tolDC in vivo, and further discusses on possibility and limitation on each strategy. This synthesis provides new perspectives on development of novel therapeutic approaches for SLE and other autoimmune diseases.


2015 ◽  
Vol 6 ◽  
Author(s):  
Torres Baeza Andy ◽  
Vega Tapia Fabián ◽  
Mackern-Oberti Juan P. ◽  
Viviani Garcia Paola ◽  
Pereira Garcés Jaime ◽  
...  

2012 ◽  
Vol 71 (Suppl 1) ◽  
pp. A34.1-A34
Author(s):  
Ahsen Morva ◽  
Sébastien Lemoine ◽  
Achouak Achour ◽  
Alain Saraux ◽  
Jacques-Olivier Pers ◽  
...  

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1039.2-1040
Author(s):  
N. Dostanko ◽  
V. Yagur ◽  
R. Goncharova ◽  
E. Siniauskaya ◽  
T. Zybalova

Background:Systemic lupus erythematosus (SLE) has a significant genetic predisposition. Many genetic variants of susceptibility to SLE have been published and analyzed, but the clinical and functional significance of the various genotypes has not yet been clearly defined [1].Objectives:To estimate the association between some of non-HLA gene polymorphisms such as STAT4 rs7574865, RUNX1 rs9979383, IL6 rs1800795, IL6R rs2228145, IL6R rs4845618 and susceptibility to SLE in Belarusian population as well as some disease manifestations.Methods:We examined 383 healthy blood donors and 54 SLE patients (18-72 years old, median age 35) classified according to the 1997 American College of Rheumatology (ACR) revised classification criteria [2]. Deoxyribonucleic acid was extracted from peripheral blood samples by phenol-chloroform method. Genotyping was performed by real-time PCR with fluorescent probes. Differences of distribution of all the single nucleotide polymorphism (SNP) genotypes and their associations with secondary antiphospholipid syndrom (APS) and lupus arthritis were analyzed using Pearson χ2 (χ2) and two-way Fisher exact test (F, p2-t). Diagnostic odds ratio (dOR), likelihood ratio of positive (LR +) and negative (LR –) tests and corresponding 95% confidence intervals (CI) were also calculated.Results:We revealed significant difference in STAT4 rs7574865 genotypes in SLE patients and healthy donors (χ2=8,27, р=0,016) with significant increase of ТТ genotype frequency in SLE patients vs healthy donors (χ2=6.83 p=0.009; p2-t =0.020; dOR=3.78 (CI95% 1.36-10.55); LR+ =3.44 (CI95% 1.35-8.71); LR– =0.91 (CI95% 0.83-0.98)). Lupus arthritis was more common in risk TT-genotype SLE carriers than in other SLE patients (χ2=5.902 p=0.015; p2-t =0.027).We revealed significant increase of СТ genotype (RUNX1 rs9979383) in healthy donors vs SLE patients (χ2=4.14; p=0.042; dOR=0.53 (CI95% 0.29-0.98); LR+ =0.69 (CI95% 0.45-0.99); LR– =1.3 (CI95% 1.01-1,56)). Lupus arthritis was more common in SLE СТ-genotype carriers than in other SLE patients (χ2=4.66 p=0.031; p2-t =0.058).Significant differences in IL6 rs1800795, IL6R rs2228145 and IL6R rs4845618 genotypes distribution between studied groups were not found (χ2, p=0.427, p=0.559 and p=0.407, correspondingly) but GG-genotype (IL6 rs1800795) carriership in SLE patients was associated with increased APS frequency (χ2=4.45, p=0.035; dOR=0.19 (CI95% 0.04-0.9); LR+ =0.28 (CI95% 0.07-0.93); LR– =1.41 (CI95% 1.03-1.64).Conclusion:Our data suggest the susceptibility to SLE in ТТ genotype of STAT4 rs7574865 polymorphism, protective role of СТ genotype of RUNX1 rs9979383 for SLE and association between GG-genotype of IL6 rs1800795 and APS in SLE patients in Belarusian population. Lupus arthritis was associated with ТТ genotype of STAT4 rs7574865 and СТ genotype of RUNX1 rs9979383.References:[1]Chen L, Morris DL, Vyse TJ. Genetic advances in systemic lupus erythematosus: an update. Curr Opin Rheumatol 2017;29:423–33.[2]Hochberg MC. Updating the American College of Rheumatology Revised Criteria for the classification of Systemic Lupus Erythematosus. Arthritis Rheum 1997;40:1725.Disclosure of Interests:None declared


2015 ◽  
Vol 112 (45) ◽  
pp. E6195-E6204 ◽  
Author(s):  
Teja Celhar ◽  
Richard Hopkins ◽  
Susannah I. Thornhill ◽  
Raquel De Magalhaes ◽  
Sun-Hee Hwang ◽  
...  

Glomerulonephritis is a common and debilitating feature of systemic lupus erythematosus (SLE). The precise immune mechanisms that drive the progression from benign autoimmunity to glomerulonephritis are largely unknown. Previous investigations have shown that a moderate increase of the innate Toll-like receptor 7 (TLR7) is sufficient for the development of nephritis. In these systems normalization of B-cell TLR7 expression or temporal depletion of plasmacytoid dendritic cells (pDCs) slow progression; however, the critical cell that is responsible for driving full immunopathology remains unidentified. In this investigation we have shown that conventional DC expression of TLR7 is essential for severe autoimmunity in the Sle1Tg7 model of SLE. We show that a novel expanding CD11b+ conventional DC subpopulation dominates the infiltrating renal inflammatory milieu, localizing to the glomeruli. Moreover, exposure of human myeloid DCs to IFN-α or Flu increases TLR7 expression, suggesting they may have a role in self-RNA recognition pathways in clinical disease. To our knowledge, this study is the first to highlight the importance of conventional DC-TLR7 expression for kidney pathogenesis in a murine model of SLE.


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