ArticleGenes2021
Paracellular and Transcellular Leukocytes Diapedesis Are Divergent but Interconnected Evolutionary Events.
Article in Genes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
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- In vivo methods for imaging blood-brain barrier function and dysfunction.European journal of nuclear medicine and molecular imaging · 2023Review
- The Journey of Cancer Cells to the Brain: Challenges and Opportunities.International journal of molecular sciences · 2023Review
- Investigation of the Molecular Evolution of Treg Suppression Mechanisms Indicates a Convergent Origin.Current issues in molecular biology · 2023Article
- Adera2.0: A Drug Repurposing Workflow for Neuroimmunological Investigations Using Neural Networks.Molecules (Basel, Switzerland) · 2022Article
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- Cytokines in the Brain and Neuroinflammation: We Didn't Starve the Fire!Pharmaceuticals (Basel, Switzerland) · 2022Review
- The Interleukin-1 (IL-1) Superfamily Cytokines and Their Single Nucleotide Polymorphisms (SNPs).Journal of immunology research · 2022Review
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- Emerging Approaches to Understanding Microvascular Endothelial Heterogeneity: A Roadmap for Developing Anti-Inflammatory Therapeutics.International journal of molecular sciences · 2021Review
- Interleukins and Interleukin Receptors Evolutionary History and Origin in Relation to CD4+ T Cell Evolution.Genes · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Infiltration of the endothelial layer of the blood-brain barrier by leukocytes plays a critical role in health and disease. When passing through the endothelial layer during the diapedesis process lymphocytes can either follow a paracellular route or a transcellular one. There is a debate whether these two processes constitute one mechanism, or they form two evolutionary distinct migration pathways. We used artificial intelligence, phylogenetic analysis, HH search, ancestor sequence reconstruction to investigate further this intriguing question. We found that the two systems share several ancient components, such as RhoA protein that plays a critical role in controlling actin movement in both mechanisms. However, some of the key components differ between these two transmigration processes. CAV1 genes emerged during Trichoplax adhaerens, and it was only reported in transcellular process. Paracellular process is dependent on PECAM1. PECAM1 emerged from FASL5 during Zebrafish divergence. Lastly, both systems employ late divergent genes such as ICAM1 and VECAM1. Taken together, our results suggest that these two systems constitute two different mechanical sensing mechanisms of immune cell infiltrations of the brain, yet these two systems are connected. We postulate that the mechanical properties of the cellular polarity is the main driving force determining the migration pathway. Our analysis indicates that both systems coevolved with immune cells, evolving to a higher level of complexity in association with the evolution of the immune system.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.