The role of tolerogenic dendritic cells in systematic lupus erythematosus progression and remission

Mohammadi, Bita; Saghafi, Mohammadreza; Faraj, Tola Abdulsattar; Kheder, Ramiar Kamal; Abdulabbas, Hadi Sajid; Esmaeili, Seyed‐Alireza

doi:10.1016/j.intimp.2022.109601

Cited by 9 publications

(10 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro studies have confirmed that there are significant phenotypic and functional abnormalities of mDC in SLE patients 33‐35 . To reverse mDC dysfunction and induce its immune tolerance is an important way to maintain the immune homeostasis of SLE 36‐40 . A recent study revealed that IL‐10‐treated mDCs could exhibit tolerogenic signature 41 .…”

Section: Discussionmentioning

confidence: 99%

“…[33][34][35] To reverse mDC dysfunction and induce its immune tolerance is an important way to maintain the immune homeostasis of SLE. [36][37][38][39][40] A recent study revealed that IL-10-treated mDCs could exhibit tolerogenic signature. 41 An animal study confirmed that a benzenediamine derivative could inhibit mDC activation induced by TLR ligands, and reduce the severity of lupus-like syndrome in MRLlpr/lpr mice.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Vitamin D3 mitigates autoimmune inflammation caused by activation of myeloid dendritic cells in SLE

Li,

Luo,

Lin

et al. 2023

Experimental Dermatology

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is an autoimmune disease in which defective T cells, immune complex deposition and other immune system alterations contribute to pathological changes of multiple organ systems. The vitamin D metabolite c is a critical immunomodulator playing pivotal roles in the immune system. Epidemiological evidence indicates that vitamin D deficiency is correlated with the severity of SLE. Our aim is to investigate the effects of 1,25(OH)2D3 (VitD3) on the activation of myeloid dendritic cells (mDCs) by autologous DNA‐containing immune complex (DNA‐ICs), and the effects of VitD3 on immune system balance during SLE. We purified DNA‐ICs from the serum of SLE patients and isolated mDCs from normal subjects. In vitro studies showed that DNA‐ICs were internalized and consumed by mDCs. VitD3 blocked the effects of DNA‐ICs on RelB, IL‐10 and TNF‐α in mDCs. Further analysis indicated that DNA‐ICs stimulated histone acetylation in the RelB promoter region, which was inhibited by VitD3. Knockdown of the histone deacetylase 3 gene (HDAC3) blocked these VitD3‐mediated effects. Co‐culture of mDCs and CD4+ T cells showed that VitD3 inhibited multiple processes mediated by DNA‐ICs, including proliferation, downregulation of IL‐10, TGF‐β and upregulation of TNF‐α. Moreover, VitD3 could also reverse the effects of DNA‐IC‐induced imbalance of CD4+ CD127− Foxp3+ T cells and CD4+ IL17+ T cells. Taken together, our results indicated that autologous DNA‐ICs stimulate the activation of mDCs in the pathogenesis of SLE, and VitD3 inhibits this stimulatory effects of DNA‐ICs by negative transcriptional regulation of RelB gene and maintaining the Treg/Th17 immune cell balance. These results suggest that vitamin D may have therapeutic value for the treatment of SLE.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vitamin D3 mitigates autoimmune inflammation caused by activation of myeloid dendritic cells in SLE

Li,

Luo,

Lin

et al. 2023

Experimental Dermatology

View full text Add to dashboard Cite

show abstract

“…Finally, unraveling the metabolic underpinnings behind DC tolerogenicity may also provide new insights into how DC-based therapies could be improved. There have been several clinical trials in which the use of ex vivo or in vivo generated tolDCs has been evaluated for treatment of autoimmune diseases, Crohn's disease, or to prevent transplant rejection [2][3][4] , unfortunately thus far, with variable success rates. Therefore, our work does not only provide new fundamental insights into the metabolic underpinnings of DC-driven tolerogenic responses, but also provides a rationale to explore AMPK as a potential actionable target for the generation of tolDCs for clinical purposes.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, promoting tolerogenic DCs (tolDCs) could be an interesting therapeutic strategy for inflammatory diseases. Although several clinical studies have already confirmed the safety of tolDC-based therapies, the clinical benefits are currently limited, in part due to impaired long-lasting maintenance of the tolerogenic state [2][3][4] . Novel insights into the processes that drive and shape DC tolerogenicity are therefore instrumental for devising new strategies to increase efficacy of tolDC-based therapies.…”

Section: Introductionmentioning

confidence: 99%

AMPK activation induces RALDH^hightolerogenic dendritic cells through rewiring of glucose and lipid metabolism

Brombacher

Patente

Ham

et al. 2023

Preprint

View full text Add to dashboard Cite

It is well known that dendritic cell (DC) activation and function are underpinned by profound changes in cellular metabolism. Several studies indicate that the ability of DCs to promote tolerance is dependent on catabolic metabolism. The AMP-activated kinase (AMPK) is a central nutrient and energy sensor whose activation promotes catabolism while inhibiting ATP-consuming anabolic pathways. Yet the contribution of AMPK activation to DC tolerogenicity remains unknown. Here, we show that AMPK activation renders human monocyte-derived DCs tolerogenic as evidenced by an enhanced ability to drive differentiation of regulatory T cells, a process dependent on increased RALDH activity. This is accompanied by a number of distinct metabolic changes, in particular increased breakdown of glycerophospholipids, enhanced mitochondrial fission-dependent fatty acid oxidation, and upregulated glucose catabolism. This metabolic rewiring is functionally important as we found interference with these metabolic processes to reduce to various degrees AMPK-induced RALDH activity as well as the tolerogenic capacity of moDCs. Altogether, our findings reveal a key role for AMPK signaling in shaping DC tolerogenicity, and suggest that AMPK may serve as new target to direct DC-driven immune responses in therapeutic settings.

show abstract

“…These antibodies eventually form an immune complex that causes complications such as lupus nephritis 42,79,80 . Various organs can be affected during the different stages of lupus, leading to distinct clinical manifestations in each case 81–83 . The level of CTLA4 expression potentially plays a role in the vulnerability of individuals to autoimmune disorders like lupus.…”

Section: The Role Of Ctla–cd80/86 Interaction In Autoimmune Diseasesmentioning

confidence: 99%

A better understanding of the role of the CTLA–CD80/86 axis in the treatment of autoimmune diseases

Darvish,

Kheder,

Faraj

et al. 2023

Cell Biochemistry & Function

Self Cite

View full text Add to dashboard Cite

Autoimmune diseases are diseases in which the regulatory mechanisms of the immune response are disturbed. As a result, the body loses self‐tolerance. Since one of the main regulatory mechanisms of the immune response is the CTLA4–CD80/86 axis, this hypothesis suggests that autoimmune diseases potentially share a similar molecular basis of pathogenesis. Hence, investigating the CTLA4–CD80/86 axis may be helpful in finding an appropriate treatment strategy. Therefore, this study aims to investigate the molecular basis of the CTLA4–CD80/86 axis in the regulation of the immune response, and then its role in developing some autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. As well, the main therapeutic strategies affecting the CTLA4–CD80/86 axis have been summarized to highlight the importance of this axis in management of autoimmune diseases.

show abstract

The role of tolerogenic dendritic cells in systematic lupus erythematosus progression and remission

Cited by 9 publications

References 110 publications

Vitamin D3 mitigates autoimmune inflammation caused by activation of myeloid dendritic cells in SLE

Vitamin D3 mitigates autoimmune inflammation caused by activation of myeloid dendritic cells in SLE

AMPK activation induces RALDH^hightolerogenic dendritic cells through rewiring of glucose and lipid metabolism

A better understanding of the role of the CTLA–CD80/86 axis in the treatment of autoimmune diseases

Contact Info

Product

Resources

About

The role of tolerogenic dendritic cells in systematic lupus erythematosus progression and remission

Cited by 9 publications

References 110 publications

Vitamin D3 mitigates autoimmune inflammation caused by activation of myeloid dendritic cells in SLE

Vitamin D3 mitigates autoimmune inflammation caused by activation of myeloid dendritic cells in SLE

AMPK activation induces RALDHhightolerogenic dendritic cells through rewiring of glucose and lipid metabolism

A better understanding of the role of the CTLA–CD80/86 axis in the treatment of autoimmune diseases

Contact Info

Product

Resources

About

AMPK activation induces RALDH^hightolerogenic dendritic cells through rewiring of glucose and lipid metabolism