Perivascular stromal cells: Directors of tissue immune niches

Abstract

Organs are comprised of diverse non-hematopoietic cells, including epithelial cells that form the internal and external layers of tissue surfaces and barriers, endothelial cells that comprise the blood and lymphatic vasculature, and stromal structural cells. Structural cells are classically thought of as "tissue glue," producing and remodeling extracellular matrix (ECM) and secreting other signals that provide passive support and form to tissues. However, recent findings have highlighted novel roles for structural cells as regulators of tissue immunity. 1 This immunoregulatory function is best studied in secondary lymphoid organs, such as lymph nodes, spleen, and mucosal associated lymphoid tissues, where diverse structural cell subsets regulate the function of adaptive lymphocytes and dendritic cells. [2][3][4][5][6] Not surprisingly, structural cells in non-lymphoid tissues are also critical regulators of both innate and adaptive

Local CCL18 and CCL21 expand lung fibrovascular niches and recruit lymphocytes, leading to tertiary lymphoid structure formation in prolonged COVID-19

“…Two of these clusters, C5 and C9, represented tissue areas with a stroma-enriched, vascular-associated signature. C5 was characterized by transcripts related to contractility and cytoskeleton rearrangements along with strong expression of ACTA2, indicative of intermediate-to-large vessels 1 . C9, in addition to that, showed the strongest expression of transcripts related to complement activation and endothelial identity.…”

“…S4C), and could reflect different maturation states of the ongoing fibrosis with a transition from microenvironments characterized by a more endothelial-dominated towards a mesenchymal signature, a process known as endothelial to mesenchymal transition (EndMT) 20 . Accordingly, C5 showed features of constitutive connective tissue associated with intermediate-to-large vessels 1 , while C9 also included endothelial-related genes, suggestive of recently generated, capillary-rich fibrous tissue 21 , and showed a strong expression of CCL21 (Fig. S4A-C and Fig.…”

“…Perivascular niches represent specialized microenvironments in various organs, where immune cells come into contact with stromal cells, in order to exchange information about the state of the tissue and modulate immune responses 1 . Acute respiratory distress syndrome (ARDS) is the main cause of death in the acute infection phase of COVID-19 2 , coursing with severe diffuse alveolar damage (DAD), endothelial disruption and immune cell infiltration in the lungs.…”

Functional Recognition Theory and Type 2 Immunity: Insights and Uncertainties

“…In addition, genome-wide association studies in humans have found that polymorphisms in IL-33 and the IL-33 receptor are associated with the development of allergic asthma (33,34). Although there are multiple cellular sources of DAMPs, epithelial cells and adventitial stromal cells represent major sites of DAMP production, indicating specialized roles of these structural cells in sensing noxious stimuli and tissue stress (35,36). Notably, while the above DAMPs play an important role in type 2 immunity, genetic deletion of individual DAMPs causes a reduction, but not complete abrogation, of type 2 immunity (27,3741).…”

One of the Primary Functions of Tissue-Resident Pluripotent Pericytes Cells May Be to Regulate Normal Organ Growth and Maturation: Implications for Attempts to Repair Tissues Later in Life

“…However, not all of the pericytes may be what has been called MSC, but their heterogeneity may also represent other cell types [ 44 ]. The role of the neural elements is not clear as following transplantation of an organ such as a liver, the nerves have been transected and there does not appear to be an overt loss of function [ 45 ].…”