Dendritic Cell Accumulation in the Gut and Central Nervous System Is Differentially Dependent on α4 Integrins

Sie, Christopher; Pérez, Laura García; Kreutzfeldt, Mario; Potthast, Maria; Ohnmacht, Caspar; Merkler, Doron; Huber, Samuel; Krug, Anne; Korn, Thomas

doi:10.4049/jimmunol.1900468

Cited by 7 publications

(10 citation statements)

References 61 publications

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“…A crucial role of α 4 β 1 -integrins for CNS entry was recently also confirmed for mouse plasmacytoid DCs ( 125 ) as well as monocyte-derived DCs ( 126 ). Interestingly, steady-state migration of conventional and plasmacytoid DCs was found to be independent of α 4 integrins ( 126 ), suggesting α 4 -integrin-mediated DC migration across the BBB to be a mechanism restricted to neuroinflammatory conditions. On the other hand it was shown that myeloid cells do not rely on β 1 -integrins to infiltrate the CNS during EAE in mice ( 127 ), underscoring that myeloid cells may use pleiotropic mechanisms to cross the BBB.…”

Section: Innate Immune Cellsmentioning

confidence: 76%

“…In vivo live cell imaging of the spinal cord microvasculature during EAE in mice demonstrated a prominent involvement of α 4 β 1integrins in mediating DC arrest in inflamed spinal cord microvessels (124). A crucial role of α 4 β 1 -integrins for CNS entry was recently also confirmed for mouse plasmacytoid DCs (125) as well as monocyte-derived DCs (126). Interestingly, steady-state migration of conventional and plasmacytoid DCs was found to be independent of α 4 integrins (126), suggesting α 4 -integrin-mediated DC migration across the BBB to be a mechanism restricted to neuroinflammatory conditions.…”

Section: Monocytes and Dendritic Cellsmentioning

confidence: 92%

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Immune cell trafficking across the blood-brain barrier in the absence and presence of neuroinflammation

2020

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To maintain the homeostatic environment required for proper function of CNS neurons the endothelial cells of CNS microvessels tightly regulate the movement of ions and molecules between the blood and the CNS. The unique properties of these blood vascular endothelial cells are termed blood-brain barrier (BBB) and extend to regulating immune cell trafficking into the immune privileged CNS during health and disease. In general, extravasation of circulating immune cells is a multi-step process regulated by the sequential interaction of adhesion and signalling molecules between the endothelial cells and the immune cells. Accounting for the unique barrier properties of CNS microvessels, immune cell migration across the BBB is distinct and characterized by several adaptations. Here we describe the mechanisms that regulate immune cell trafficking across the BBB during immune surveillance and neuroinflammation, with a focus on the current state-of-the-art in vitro and in vivo imaging observations.

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Section: Innate Immune Cellsmentioning

confidence: 76%

Section: Monocytes and Dendritic Cellsmentioning

confidence: 92%

Immune cell trafficking across the blood-brain barrier in the absence and presence of neuroinflammation

2020

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“…Though additional evidence is needed, the existing results have demonstrated that compartmentalized IFN responses are observed in COVID-19 patients. This observation can be further explained by the increased number of IFN producing pDCs, which may have migrated from peripheral blood to lung and gut tissue due to induction of migratory molecules such as α4β7 [41] , [42] , [43] . T cells and pDCs migrate to gut tissues with their ability to bind α4β7 with MadCAM1 receptor and may cause inflammation [41] , [42] , [43] .…”

Section: Reduced Type I Ifn Responses and Mechanisms To Escape Antiviral Responses During Corona Viral Infectionsmentioning

confidence: 99%

“…This observation can be further explained by the increased number of IFN producing pDCs, which may have migrated from peripheral blood to lung and gut tissue due to induction of migratory molecules such as α4β7 [41] , [42] , [43] . T cells and pDCs migrate to gut tissues with their ability to bind α4β7 with MadCAM1 receptor and may cause inflammation [41] , [42] , [43] . Aggravated inflammation due to increased production of cytokines, chemokine mediators and hyper activity of immune cells including pDCs in lung tissue may cause acute respiratory distress syndrome (ARDS), and sustained inflammation may lead to multiple organ failure and ultimately death in COVID-19 patients [44] .…”

Section: Reduced Type I Ifn Responses and Mechanisms To Escape Antiviral Responses During Corona Viral Infectionsmentioning

confidence: 99%

Role of toll-like receptor 7/8 pathways in regulation of interferon response and inflammatory mediators during SARS-CoV2 infection and potential therapeutic options

Dyavar¹,

Singh²,

Emani³

et al. 2021

Biomedicine & Pharmacotherapy

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) is the causative agent of Corona Virus Disease 2019 (COVID-19). Lower production of type I and III interferons and higher levels of inflammatory mediators upon SARS-CoV2 infection contribute to COVID-19 pathogenesis. Optimal interferon production and controlled inflammation are essential to limit COVID-19 pathogenesis. However, the aggravated inflammatory response observed in COVID-19 patients causes severe damage to the host and frequently advances to acute respiratory distress syndrome (ARDS). Toll-like receptor 7 and 8 (TLR7/8) signaling pathways play a central role in regulating induction of interferons (IFNs) and inflammatory mediators in dendritic cells. Controlled inflammation is possible through regulation of TLR mediated response without influencing interferon production and may reduce COVID-19 pathogenesis. This review focuses on inflammatory mediators contribute to pathogenic effects and the role of TLR pathways in the induction of interferon and inflammatory mediators and their contribution to COVID-19 pathogenesis. We conclude that potential TLR7/8 agonists inducing antiviral interferon response and control inflammation are important therapeutic options to effectively eliminate SARS-CoV2 induced pathogenesis. Ongoing and future studies may provide additional evidence on their safety and efficacy to treat COVID-19 pathogenesis.

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“…During clinical blood transfusion, it was usually classified as the anti-JMH autoantibody in acquired JMH-negative patients. Early studies have shown that inherited JMH-negative patients can be immunized to produce anti-JMH antibodies, providing positive results in the monocyte function test and significantly decreasing the survival time of 51 Cr-labelled JMH-positive erythrocytes in patients [18,28]. Additionally, it has been reported that transfusion of JMH-positive RBCs in JMH-negative patients with a positive anti-JMH alloantibody led to an acute haemolytic transfusion reaction [16,26].…”

Section: Introductionmentioning

confidence: 99%

Anti-JMH alloantibody in inherited JMH-negative patients leads to immunogenic destruction of JMH-positive RBCs

Zhang

Wei

Chen

et al. 2021

Clinical and Experimental Immunology

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The clinical significance of the specific anti-John Milton Hagen (JMH) alloantibody in inherited JMH-negative patients remains unclear. During clinical blood transfusion, it is often classified as an anti-JMH autoantibody in acquired JMH-negative patients, which might further lead to the occurrence of haemolysis events. In this study, we found that the proportion of inherited JMH-negative people in the Guangzhou population was 0.41%, based on the study of 243 blood samples by flow cytometry. Gene sequencing analysis revealed two novel variants located in exon 11 (c.1348G>A, p.Ala449Thr) and exon 14 (c.1989G>T, p.Leu663Phe). Specific antigen presentation showed that JMH-positive RBCs (red blood cells) could be internalized by SEMA7A −/− dendritic cells (DCs) and that SEMA7A −/− DCs activated by the semaphorin 7a (Sema7a) protein or JMH-positive erythrocytes further induced activation of CD4 + T cells to secrete interferon (IFN)-γ. Transfusion of JMH-positive RBCs could lead to the production of the specific anti-JMH alloantibody in Sema7a knock-out (KO) C57 mice. After erythrocyte sensitization, complement C3 was specifically fixed, causing the destruction of JMH-positive erythrocytes. The anti-JMH alloantibody caused immunological destruction of JMH-positive erythrocytes and promoted the clearance of JMH-positive RBCs. We should be cautious when making conclusions about the clinical significance of the anti-JMH alloantibody.

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Dendritic Cell Accumulation in the Gut and Central Nervous System Is Differentially Dependent on α4 Integrins

Cited by 7 publications

References 61 publications

Immune cell trafficking across the blood-brain barrier in the absence and presence of neuroinflammation

Immune cell trafficking across the blood-brain barrier in the absence and presence of neuroinflammation

Role of toll-like receptor 7/8 pathways in regulation of interferon response and inflammatory mediators during SARS-CoV2 infection and potential therapeutic options

Anti-JMH alloantibody in inherited JMH-negative patients leads to immunogenic destruction of JMH-positive RBCs

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