Mesenchymal perivascular cells in immunity and disease

Abstract

The mesenchymal microenvironment is increasingly recognized as a major player in immunity. Here we focus on mesenchymal cells located within or in proximity to the blood vessels wall, which include pericytes, adventitial fibroblasts and mesenchymal stromal cells. We discuss recent evidence that these cells play a role in tissue homeostasis, immunity and inflammatory pathologies by multiple mechanisms, including vascular modulation, leucocyte migration, activation or survival in the perivascular space and differentiation into specialized 'effector' mesenchymal cells essential for tissue repair and immunity, such as myofibroblasts and lymphoid stromal cells. When dysregulated, these responses contribute to inflammatory and fibrotic diseases.

Figure 1

The perivascular space around capillaries (a) and arteries (b) at steady-state and after inflammation.

Figure 2

Proposed functions for mesenchymal cells of the perivascular niche. In addition to their vascular role, pericytes and adventitial cells regulate inflammation and tissue homeostasis/repair by regulating recruitment and/or activity of immune cells, in particular myeloid cells and innate lymphoid cells. Furthermore, specific subsets of perivascular mesenchymal cells can act as progenitors for matrix-producing fibroblasts (following tissue injury) or lymphoid stromal cells such as TRCs, FDC, MRCs in lymphoid organs development. MSC: mesenchymal stromal cells; TRC: T-zone reticular cells; FDC: Follicular dendritic cells; MRC: marginal reticular cells.