Epigenetic Programing of B-Cell Lymphoma by BCL6 and Its Genetic Deregulation

Yang, Haopeng; Green, Michael R.

doi:10.3389/fcell.2019.00272

Cited by 36 publications

(36 citation statements)

References 83 publications

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“…In females, 1426 genes were upregulated in LPS uninjured compared with VEH uninjured, and 79 genes were upregulated in LPS injured compared with VEH injured. C57Bl/6J female uninjured LPS joints showed similarities to the corresponding males as reflected in the upregulation of inflammatory and immune response genes such as Tlr5 , Bcl6 , ( 48 ) Cxcl1 , ( 49 ) Il15 , ( 50 ) Prkca , ( 51 ) Ptges , ( 52 ) and Saa3 ( 53 ) (Fig. 5 A , B ).…”

Section: Resultsmentioning

confidence: 90%

LPS-Induced Inflammation Prior to Injury Exacerbates the Development of Post-Traumatic Osteoarthritis in Mice

Mendez

Sebastian

Murugesh

et al. 2020

Journal of Bone and Mineral Research

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Osteoarthritis (OA) is a debilitating and painful disease characterized by the progressive loss of articular cartilage. Post-traumatic osteoarthritis (PTOA) is an injury-induced type of OA that persists in an asymptomatic phase for years before it becomes diagnosed in~50% of injured individuals. Although PTOA is not classified as an inflammatory disease, it has been suggested that inflammation could be a major driver of PTOA development. Here we examined whether a state of systemic inflammation induced by lipopolysaccharide (LPS) administration 5-days before injury would modulate PTOA outcomes. RNA-seq analysis at 1-day post-injury followed by micro-computed tomography (μCT) and histology characterization at 6 weeks post-injury revealed that LPS administration causes more severe PTOA phenotypes. These phenotypes included significantly higher loss of cartilage and subchondral bone volume. Gene expression analysis showed that LPS alone induced a large cohort of inflammatory genes previously shown to be elevated in synovial M1 macrophages of rheumatoid arthritis (RA) patients, suggesting that systemic LPS produces synovitis. This synovitis was sufficient to promote PTOA in MRL/MpJ mice, a strain previously shown to be resistant to PTOA. The synovium of LPS-treated injured joints displayed an increase in cellularity, and immunohistological examination confirmed that this increase was in part attributable to an elevation in type 1 macrophages. LPS induced the expression of Tlr7 and Tlr8 in both injured and uninjured joints, genes known to be elevated in RA. We conclude that inflammation before injury is an important risk factor for the development of PTOA and that correlating patient serum endotoxin levels or their state of systemic inflammation with PTOA progression may help develop new, effective treatments to lower the rate of PTOA in injured individuals.

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Section: Resultsmentioning

confidence: 90%

LPS-Induced Inflammation Prior to Injury Exacerbates the Development of Post-Traumatic Osteoarthritis in Mice

Mendez

Sebastian

Murugesh

et al. 2020

Journal of Bone and Mineral Research

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“…The majority of the ~ 120 transcription factors with BTB domains, for example, form homodimers to engage their proper effector proteins impacting transcription. The transcription repressor BCL6, which is mutated in B‐cell lymphomas (Yang & Green, 2019), binds to a SMRT, BCOR, and NCoR co‐repressor through each of its BTB subunits (Ahmad et al, 2003; Ghetu et al, 2008). BCL6, however, also forms aberrant heterodimers that are unable to engage co‐repressors and impede gene regulation (Mena et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Ubiquitin‐dependent regulation of transcription in development and disease

Mark

Rapé

2021

EMBO Reports

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Transcription is an elaborate process that is required to establish and maintain the identity of the more than two hundred cell types of a metazoan organism. Strict regulation of gene expression is therefore vital for tissue formation and homeostasis. An accumulating body of work found that ubiquitylation of histones, transcription factors, or RNA polymerase II is crucial for ensuring that transcription occurs at the right time and place during development. Here, we will review principles of ubiquitin‐dependent control of gene expression and discuss how breakdown of these regulatory circuits leads to a wide array of human diseases.

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“…The reduction in GC B cell numbers, was not due to changes in the TFH cell population ( Figure 5A ) or in levels of IL-6, IL-1β, and IL-21, known to be involved in the GC reaction ( Figures 5B–D ). Similarly, expression levels of Bcl6 , a crucial transcription factor for TFH and GC B cells ( 33 – 35 ), was unchanged ( Figure 5E ).…”

Section: Resultsmentioning

confidence: 92%

Partial Protection From Lupus-Like Disease by B-Cell Specific Type I Interferon Receptor Deficiency

et al. 2021

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Systemic lupus erythematosus (SLE) is an autoimmune disease that can present with many different permutations of symptom presentation. A large subset of SLE patients have been shown to present with elevated interferon stimulated gene (ISG) expression, and Type I IFNs (IFNαβ) have been shown to drive disease in murine models through global IFNα Receptor (IFNAR) knockouts. However, the disease contribution of distinct immune cell subsets in response to constitutively increased levels of IFNαβ is not fully understood. We utilized a B-cell specific IFNAR knockout (BΔIFNAR) on the B6.Nba2 spontaneous-lupus background to determine the contribution of IFNαβ stimulated B cells in disease. We found that IFNαβ signaling in B cells is driving increased splenomegaly, increased populations of activated B cells, and increased populations of germinal center (GC) B cells, memory B cells, and plasma blasts/cells, but did not affect the development of glomerulonephritis and immune-complex deposition. IFNAR expression by B cells also drove production of anti-chromatin IgG, and anti-dsDNA and -nRNP IgG and IgG2C auto-antibody levels, as well as increased Bcl2 expression, affecting GC B cell survival in B6.Nba2 mice.

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Epigenetic Programing of B-Cell Lymphoma by BCL6 and Its Genetic Deregulation

Cited by 36 publications

References 83 publications

LPS-Induced Inflammation Prior to Injury Exacerbates the Development of Post-Traumatic Osteoarthritis in Mice

LPS-Induced Inflammation Prior to Injury Exacerbates the Development of Post-Traumatic Osteoarthritis in Mice

Ubiquitin‐dependent regulation of transcription in development and disease

Partial Protection From Lupus-Like Disease by B-Cell Specific Type I Interferon Receptor Deficiency

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