This Research Topic is the second volume of the “Effects of Cell Interactions at the Endothelium in Leukocyte Differentiation and Polarization during Inflammation” Community Series. Please see volume I here.

A complex exchange of signals between endothelial cells and tissues occurs during steady-state and in inflammatory conditions. These interactions involve numerous cell types including an active contribution from endothelial cells and occur on both sides of the endothelial monolayer. In addition to functioning as selective permeability barriers, it is increasingly recognized that local cell attraction to endothelial cells provides the potential for focal interactions between relevant cells. In this context, cellular interactions taking place at the surface of the endothelium and within the perivascular spaces are thought to initiate crucial steps in the generation and shaping of immune responses.

Blood elements (such as leukocytes, platelets, and vesicles) converge to the barrier formed by the endothelium where perivascular (such as macrophages, pericytes) initiate, convey, and/or amplify signals revealing tissue status. The innate and adaptative functions of endothelial cells themselves together with the immune functions of assembled cells at a focal point in capillaries create the potential for exchange of signals and dynamic fine tuning of responses through cell programming and cell selection. The resulting immune response may range from inadequate immunity and/or exhaustion to excess tissue destruction and fibrosis. Productive inflammation and its resolution are critically reliant on which cells are recruited and in which order, their state of activation, and interactions between recruited cells.

Tissue-dependent signals further shape the recruitment of leukocytes to the endothelium. In the kidney for instance, in the presence of immune complexes, perivascular resident macrophages located in subendothelial spaces coupled with endothelial cells induce monocyte and neutrophil tissue infiltration, operating therefore as an anatomical and functional unit.

The goals of this Research Topic are (i) to analyze how signal integration and partnering of cell types in transendothelial migration contribute to the development of tissue inflammation and how responses are geared towards specific profiles of reactions to injury; (ii) how the interplay between cell types including, but not limited to, endothelial cells, monocytes, resident macrophages, and T and B cells dynamically governs the immune responses that take place in the tissue; (iii) in which way do integrative capacities of endothelial and subendothelial cells shape and coordinate the successive recruitment of leukocyte populations.

Manuscripts published in this research topic will provide insights into cell interactions at the endothelium in steady-state and in inflammation, in in vitro or in vivo models, and in tissue-specific settings. Although not limited to the following points, we would welcome the submissions of Original Research, Review, Minireview addressing:

- Monocyte (bulk and subsets) activation and polarization in interactions with activated endothelial cells, tissue specificity characteristics, effects of transmigration on the status of monocytes and endothelial cells

- Interactions between monocytes and lymphocytes recruited at the surface of endothelial cells and functional implications

- Contributions of various subendothelial cell types, such as macrophage populations, to the recruitment and activation of leukocytes populations at the surface of endothelial cells

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Frontiers in Immunology

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