Transcriptional control of apoptotic cell clearance by macrophage nuclear receptors

Röszer, Tamás

doi:10.1007/s10495-016-1310-x

Cited by 59 publications

(61 citation statements)

References 72 publications

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“…The cluster analysis (Table S2) indicates that there are only few transcripts that share a transcription pattern with MARCO, of which only VSIG4 and GPR34 were highly-expressed. The underlying transcriptional regulation is also consistent with data from mice, in that genes encoding known regulators of apoptotic receptors in mice, NR1H33 and PPARG (51) were also strongly-enriched in the chicken Kupffer cells. In mice, Kupffer cells are required for the elimination of senescent red blood cells and recycling of iron (52).…”

Section: Discussionsupporting

confidence: 87%

Characterisation of subpopulations of chicken mononuclear phagocytes that express TIM4 and the macrophage colony-stimulating factor receptor (CSF1R)

Bush

et al. 2018

Preprint

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The phosphatidylserine receptor, TIM4, encoded by TIMD4, mediates the phagocytic uptake of apoptotic cells. We applied anti-chicken TIM4 monoclonal antibodies, in combination with CSF1R reporter transgenes to dissect the function of TIM4 in chick (Gallus gallus). During development in ovo, TIM4 was present on the large majority of macrophages but expression became more heterogeneous post-hatch. Blood monocytes expressed KUL01, class II MHC and CSF1R-mApple uniformly. Around 50% of monocytes were positive for surface TIM4. They also expressed many other monocyte-specific transcripts at a higher level than TIM4− monocytes. In liver, highly-phagocytic TIM4hi cells shared many transcripts with mammalian Kupffer cells and were associated with uptake of apoptotic cells. Although they expressed CSF1R mRNA, Kupffer cells did not express the CSF1R-mApple transgene, suggesting that additional CSF1R transcriptional regulatory elements are required by these cells. By contrast, CSF1R-mApple was detected in liver TIM4lo and TIM4− cells which were not phagocytic and were more abundant than Kupffer cells. These cells expressed CSF1R, alongside high levels of FLT3, MHCII, XCR1 and other markers associated with conventional dendritic cells (cDC) in mice. In bursa, TIM4 was present on the cell surface of two populations. Like Kupffer cells, bursal TIM4hi phagocytes co-expressed many receptors involved in apoptotic cell recognition. TIM4lo cells appear to be a sub-population of bursal B cells. In overview, TIM4 is associated with phagocytes that eliminate apoptotic cells in the chick. In the liver, TIM4 and CSF1R reporters distinguished Kupffer cells from an abundant population of DC-like cells.

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Section: Discussionsupporting

confidence: 87%

Characterisation of subpopulations of chicken mononuclear phagocytes that express TIM4 and the macrophage colony-stimulating factor receptor (CSF1R)

Bush

et al. 2018

Preprint

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“…Different studies have shown that PPAR and LXR are activated in macrophages in response to apoptotic cells and express genes such as the cholesterol transporter ABCA1 and phospholipid transporter, phospholipid transfer protein 1 (PLTP1). Moreover, PPAR and LXR activity upregulate the expression of phagocytic receptors (Mer, CD36 and Axl) and opsonins (C1qb, Gas6, MFG-E8,) that support phagocytic activity and continuous engulfment of apoptotic bodies [118, 119]. Perhaps the most interesting feature of PPAR and LXR activation in response to efferocytosis that points towards a putative role in macrophage function is the induction of anti-inflammatory IL-10, and prevention of inflammatory cytokine production [120–122].…”

Section: Implications Of Lap In Macrophage Immunometabolismmentioning

confidence: 99%

LC3-Associated Phagocytosis and Inflammation

Heckmann

Boada-Romero

Cunha

et al. 2017

Journal of Molecular Biology

216

202

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LC3-associated phagocytosis (LAP) is a novel form of non-canonical autophagy where LC3 (microtubule-associated protein 1A/1B-light chain 3) is conjugated to phagosome membranes using a portion of the canonical autophagy machinery. The impact of LAP to immune regulation is best characterized in professional phagocytes, in particular macrophages, where LAP has instrumental roles in the clearance of extracellular particles including apoptotic cells and pathogens. Binding of dead cells via receptors present on the macrophage surface results in the translocation of the autophagy machinery to the phagosome and ultimately LC3 conjugation. These events promote a rapid form of phagocytosis that produces an “immunologically silent” clearance of the apoptotic cells. Consequences of LAP deficiency include a decreased capacity to clear dying cells and the establishment of a lupus-like autoimmune disease in mice. The ability of LAP to attenuate autoimmunity likely occurs through the dampening of pro-inflammatory signals upon engulfment of dying cells and prevention of autoantigen presentation to other immune cells. However, it remains unclear how LAP shapes both the activation and outcome of the immune response at the molecular level. Herein, we provide a detailed review of LAP and its known roles in the immune response and provide further speculation on the putative mechanisms by which LAP may regulate immune function, perhaps through the metabolic reprogramming and polarization of macrophages.

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“…In addition, the αvβ3 integrin express on phagocytes can bind to thrombospondin, helping the recognition of PS on the surface of apoptotic cells (51). Other apoptotic cell recognition receptors, such as the family of receptor tyrosine kinases Tyro3, Axl, and MerTK (TAM), also need to bind to bridge molecule to interact with PtdSer on the surface of apoptotic cells (52–54). …”

Section: Apoptosis As a Hallmark Of T Cruzi Infectionmentioning

confidence: 99%

Implication of Apoptosis for the Pathogenesis of Trypanosoma cruzi Infection

et al. 2017

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Apoptosis is induced during the course of immune response to different infectious agents, and the ultimate fate is the recognition and uptake of apoptotic bodies by neighboring cells or by professional phagocytes. Apoptotic cells expose specific ligands to a set of conserved receptors expressed on macrophage cellular surface, which are the main cells involved in the clearance of the dying cells. These scavenger receptors, besides triggering the production of anti-inflammatory factors, also block the production of inflammatory mediators by phagocytes. Experimental infection of mice with the parasite Trypanosoma cruzi shows many pathological changes that parallels the evolution of human infection. Leukocytes undergoing intense apoptotic death are observed during the immune response to T. cruzi in the mouse model of the disease. T. cruzi replicate intensely and secrete molecules with immunomodulatory activities that interfere with T cell-mediated immune responses and secretion of pro-inflammatory cytokine secretion. This mechanism of immune evasion allows the infection to be established in the vertebrate host. Under inflammatory conditions, efferocytosis of apoptotic bodies generates an immune-regulatory phenotype in phagocytes, which is conducive to intracellular pathogen replication. However, the relevance of cellular apoptosis in the pathology of Chagas’ disease requires further studies. Here, we review the evidence of leukocyte apoptosis in T. cruzi infection and its immunomodulatory mechanism for disease progression.

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Transcriptional control of apoptotic cell clearance by macrophage nuclear receptors

Cited by 59 publications

References 72 publications

Characterisation of subpopulations of chicken mononuclear phagocytes that express TIM4 and the macrophage colony-stimulating factor receptor (CSF1R)

Characterisation of subpopulations of chicken mononuclear phagocytes that express TIM4 and the macrophage colony-stimulating factor receptor (CSF1R)

LC3-Associated Phagocytosis and Inflammation

Implication of Apoptosis for the Pathogenesis of Trypanosoma cruzi Infection

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