Programmed death (PD)-1 attenuates macrophage activation and brain inflammation via regulation of fibrinogen-like protein 2 (Fgl-2) after intracerebral hemorrhage in mice

Yuan, Bangqing; Huang, Shaokuan; Gong, Shuangfeng; Wang, Feihong; Lin, Li; Su, Tonggang; Sheng, Hanchao; Shi, Hui; Ma, Kunlong; Yang, Zhao

doi:10.1016/j.imlet.2016.10.001

Cited by 18 publications

(7 citation statements)

References 35 publications

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“…PD-1 KO mice showed a slight exacerbation in two different behavioral tasks when compared to WT mice infected with ME7, which points to the possibility that PD-1 ablation is more detrimental than beneficial in the context of neurodegeneration. An exacerbation of clinical symptoms in PD-1 KO mice has been observed before in models of EAE ( Zhang and Braun, 2014 ) and intracerebral hemorrhage ( Yuan et al, 2016 ). Although we did not proceed to identify the cellular or molecular basis underlying the acceleration of prion disease pathology, it is possible that PD-1 plays a role in multiple aspects of the neuroinflammatory response or that changes are very subtle and not detectable with the here applied methods.…”

Section: Discussionsupporting

confidence: 54%

PD-1 deficiency is not sufficient to induce myeloid mobilization to the brain or alter the inflammatory profile during chronic neurodegeneration

Obst

Mancuso

Simon

et al. 2018

Brain, Behavior, and Immunity

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Section: Discussionsupporting

confidence: 54%

PD-1 deficiency is not sufficient to induce myeloid mobilization to the brain or alter the inflammatory profile during chronic neurodegeneration

Obst

Mancuso

Simon

et al. 2018

Brain, Behavior, and Immunity

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“…124 In contrast, a mouse collagenase injection ICH model has shown upregulation of PD-1 expression in the perihematomal tissues, expressed mainly on macrophages, and in PD-1 KO mice, there was significant increase in mRNA and protein expression of pro-inflammatory cytokines compared to WT ICH groups, manifesting as increased brain water content and worsened neurologic impairment in the PD-1 KO group. 125 PD-L1 administration significantly attenuated the severity of neurologic deficits, decreased cerebral edema by decreasing brain water content, and decreased hemorrhage volume. 126 PD-L1 also downsized the number of CD4 + T cells infiltrating the brain and overall percentages of Th1 and Th17 cells while increasing the overall percentages of the Th2 and regulatory T cells.…”

Section: Programmed Death-1 Pathwaymentioning

confidence: 87%

Neuroinflammation after Intracerebral Hemorrhage and Potential Therapeutic Targets

et al. 2020

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Spontaneous intracerebral hemorrhage (ICH) is a catastrophic illness causing significant morbidity and mortality. Despite advances in surgical technique addressing primary brain injury caused by ICH, little progress has been made treating the subsequent inflammatory cascade. Pre-clinical studies have made advancements identifying components of neuroinflammation, including microglia, astrocytes, and T lymphocytes. After cerebral insult, inflammation is initially driven by the M1 microglia, secreting cytokines (e.g., interleukin-1β [IL-1β] and tumor necrosis factor-α) that are involved in the breakdown of the extracellular matrix, cellular integrity, and the blood brain barrier. Additionally, inflammatory factors recruit and induce differentiation of A1 reactive astrocytes and T helper 1 (Th1) cells, which contribute to the secretion of inflammatory cytokines, augmenting M1 polarization and potentiating inflammation. Within 7 days of ICH ictus, the M1 phenotype coverts to a M2 phenotype, key for hematoma removal, tissue healing, and overall resolution of inflammation. The secretion of anti-inflammatory cytokines (e.g., IL-4, IL-10) can drive Th2 cell differentiation. M2 polarization is maintained by the secretion of additional anti-inflammatory cytokines by the Th2 cells, suppressing M1 and Th1 phenotypes. Elucidating the timing and trigger of the anti-inflammatory phenotype may be integral in improving clinical outcomes. A challenge in current translational research is the absence of an equivalent disease animal model mirroring the patient population and comorbid pathophysiologic state. We review existing data and describe potential therapeutic targets around which we are creating a bench to bedside translational research model that better reflects the pathophysiology of ICH patients.

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“…The former conditions can further develop into chronic metabolic impairments like diabetes. [24] It is worth noting, however, that the research has demonstrated that emotional stresses were majorly related to the occurrence of LADA. [3] Relative mechanisms potentially underlying the influences that we have found are further elucidated subsequently.…”

Section: Discussionmentioning

confidence: 99%

Emotional exhaustion-induced latent autoimmune diabetes in adults in a young lady

et al. 2017

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Rationale:Latent autoimmune diabetes in adults (LADA) refers to an autoimmune disorder characterized with detectable islets antibodies in the early diagnosis and increased autoimmune beta-cell failure progression. Notably, this kind of diabetes seems to be confused with other phenotypic diabetes.Patient concerns:A young woman suffered an emotional exhaustion-induced LADA, showing asthenia, polydipsia, polyuria, and visible weight loss. The patient emotionally ended a 14-year romantic relationship, leading to the emotional flooding.Diagnoses:The data from physical examination and laboratory tests exhibited as follows: glutamic acid decarboxylase antibody (GADA) = 63.83 U/mL, the fasting blood glucose (FBG) = 13.3 mmol/L, and glycated haemoglobin (HbA1c) = 10.9%. According to levels of GADA, the patient was diagnosed as LADA.Interventions:The patient was clinically treated with insulin for 3-month. Then, running, diet-control, and emotional treatment were combined, such as the patient started a new relationship.Outcomes:An emotional recovery initiated from a new romantic relationship and a baby, showing normal levels of GAD65 (27.007 IU/mL) and FBG (5.46) mmol/L.Lessons:The emotional exhaustion might play a significant role in induction of LADA. It is important that individuals should maintain optimism, cheer, and a positive attitude.

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Programmed death (PD)-1 attenuates macrophage activation and brain inflammation via regulation of fibrinogen-like protein 2 (Fgl-2) after intracerebral hemorrhage in mice

Cited by 18 publications

References 35 publications

PD-1 deficiency is not sufficient to induce myeloid mobilization to the brain or alter the inflammatory profile during chronic neurodegeneration

PD-1 deficiency is not sufficient to induce myeloid mobilization to the brain or alter the inflammatory profile during chronic neurodegeneration

Neuroinflammation after Intracerebral Hemorrhage and Potential Therapeutic Targets

Emotional exhaustion-induced latent autoimmune diabetes in adults in a young lady

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