Bcl6 modulates innate immunity by controlling macrophage activity and plays critical role in experimental autoimmune encephalomyelitis

Li, Qing; Zhou, Lei; Li, Shiqiang; Xu, Guiliang; Gu, Hongru; Li, Dali; Liu, Mingyao; Fang, Lei; Wang, Zhengyi; Han, Shuhua; Zheng, Biao

doi:10.1002/eji.201948299

Cited by 26 publications

(24 citation statements)

References 38 publications

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“…The action of anti-inflammatory Mφ is pivotal in the prevention and treatment of inflammatory-related diseases. [31][32][33] Our previous study had demonstrated that, similar to MSCs, adoptive transfer of MSCs-educated Mφ attenuated inflammation and kidney injuries in STZ-induced DN mice. 17 PGC-1α has been demonstrated to drive mitochondrial biogenesis.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Transfer from Mesenchymal Stem Cells to Macrophages Restricts Inflammation and Alleviates Kidney Injury in Diabetic Nephropathy Mice via PGC-1α Activation

Yuan

et al. 2021

Stem Cells

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Mesenchymal stem cells (MSCs) have fueled ample translation for treatment of immune-mediated diseases. Our previous study had demonstrated that MSCs could elicit macrophages (Mφ) into anti-inflammatory phenotypes, and alleviate kidney injury in diabetic nephropathy (DN) mice via improving mitochondrial function of Mφ, yet the specific mechanism was unclear. Recent evidence indicated that MSCs communicated with their microenvironment through exchanges of mitochondria. By a coculture system consisting of MSCs and Mφ, we showed that MSCs-derived mitochondria (MSCs-Mito) were transferred into Mφ, and the mitochondrial functions were improved, which contributed to M2 polarization. Furthermore, we found that MSCs-Mito transfer activated peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis. In addition, PGC-1α interacted with TFEB in high glucose-induced Mφ, leading to the elevated lysosome-autophagy, which was essential to removal of damaged mitochondria. As a result, in Mφ, the mitochondrial bioenergy and capacity to combat inflammatory response were enhanced. Whereas, the immune-regulatory activity of MSCs-Mito was significantly blocked in PGC-1α knockdown Mφ. More importantly, MSCs-Mito transfer could be observed in DN mice, and the adoptive transfer of MSCs-Mito educated Mφ (MφMito) inhibited the inflammatory response and alleviated kidney injury. However, the kidney-protective effects of MφMito were abolished when the MSCs-Mito was impaired with rotenone, and the similar results were also observed when MφMito were transfected with sipgc-1α before administration. Collectively, these findings suggested that MSCs elicited Mφ into anti-inflammatory phenotype and ameliorated kidney injury through mitochondrial transfer in DN mice, and the effects were relied on PGC-1α-mediated mitochondrial biogenesis and PGC-1α/TFEB-mediated lysosome-autophagy.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial Transfer from Mesenchymal Stem Cells to Macrophages Restricts Inflammation and Alleviates Kidney Injury in Diabetic Nephropathy Mice via PGC-1α Activation

Yuan

et al. 2021

Stem Cells

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“…CXCR5, BCL‐6) does not completely inhibit the function of germinal centres [ 98 ]. Beyond, there are substantial differences between in vivo and in vitro studies investigating T FH cells, and molecules regulating the development of T FH cells such as BCL‐6, ICOS, CXCL13, CXCR5, IL‐21/IL‐21R, PD‐1/PD‐L1 have opposite roles during EAE development [ 94 , 109 , 112 , 113 , 114 , 115 ], possibly reflecting the heterogeneity of T FH cells in different MS‐related animal models. Finally, these molecules are not specific to T FH cells and their inhibition can affect a variety of other cells and cellular interactions.…”

Section: Insights Into Elfs From Animal Studiesmentioning

confidence: 99%

Ectopic lymphoid follicles in progressive multiple sclerosis: From patients to animal models

et al. 2021

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Ectopic lymphoid follicles (ELFs), resembling germinal centre‐like structures, emerge in a variety of infectious and autoimmune and neoplastic diseases. ELFs can be found in the meninges of around 40% of the investigated progressive multiple sclerosis (MS) post‐mortem brain tissues and are associated with the severity of cortical degeneration and clinical disease progression. Of predominant importance for progressive neuronal damage during the progressive MS phase appears to be meningeal inflammation, comprising diffuse meningeal infiltrates, B‐cell aggregates and compartmentalized ELFs. However, the absence of a uniform definition of ELFs impedes reproducible and comparable neuropathological research in this field. In this review article, we will first highlight historical aspects and milestones around the discovery of ELFs in the meninges of progressive MS patients. In the next step, we discuss how animal models may contribute to an understanding of the mechanisms underlying ELF formation. Finally, we summarize challenges in investigating ELFs and propose potential directions for future research.

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“…B-cell lymphoma 6 (BCL6) is a sequence-specific transcriptional regulator that inhibits the transcription of target genes by binding to a specific DNA sequence in the promoter region ( 24 , 25 ). BCL6 serves an important role in the development of B cells, follicular Th cells and T regulatory cells, indicating its potential function in regulation of the immune response ( 26 – 28 ).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of miR‑205‑5p alleviates the inflammatory response in allergic rhinitis by targeting B‑cell lymphoma 6

et al. 2021

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allergic rhinitis (ar) is an ige-mediated upper airway disease with a high worldwide prevalence. Microrna (mir)-205-5p upregulation has been observed in ar; however, its role is poorly understood. The aim of the present study was to investigate the effect of mir-205-5p on AR-associated inflammation. To establish an AR model, BalB/c mice were sensitized using an intraperitoneal injection of ovalbumin (oVa) on days 0, 7 and 14, followed by intranasal challenge with oVa on days 21-27. a lentiviral sponge for mir-205-5p was used to downregulate mir-205-5p in vivo via intranasal administration on days 20-26. reverse transcription-quantitative Pcr revealed that mir-205-5p was upregulated in ar mice. notably, mir-205-5p knockdown reduced the frequency of nose-rubbing and sneezing, and attenuated pathological alterations in the nasal mucosa. The levels of total and OVA-specific IgE, cytokines IL-4, IL-5 and IL-13, and inflammatory cells, were decreased by miR-205-5p knockdown in ar mice. in addition, mir-205-5p knockdown inhibited nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation by reducing the expression levels of nlrP3, apoptosis associated speck like protein containing a card, cleaved caspase-1 and il-1β by western blot analysis. B-cell lymphoma 6 (BCL6) was confirmed as a target of miR-205-5p by luciferase reporter assay. In conclusion, the present findings suggested that mir-205-5p knockdown may attenuate the inflammatory response in AR by targeting BCL6, which may be a potential therapeutic target for ar.

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Bcl6 modulates innate immunity by controlling macrophage activity and plays critical role in experimental autoimmune encephalomyelitis

Cited by 26 publications

References 38 publications

Mitochondrial Transfer from Mesenchymal Stem Cells to Macrophages Restricts Inflammation and Alleviates Kidney Injury in Diabetic Nephropathy Mice via PGC-1α Activation

Mitochondrial Transfer from Mesenchymal Stem Cells to Macrophages Restricts Inflammation and Alleviates Kidney Injury in Diabetic Nephropathy Mice via PGC-1α Activation

Ectopic lymphoid follicles in progressive multiple sclerosis: From patients to animal models

Knockdown of miR‑205‑5p alleviates the inflammatory response in allergic rhinitis by targeting B‑cell lymphoma 6

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