Stromal Cells Underlining the Paths From Autoimmunity, Inflammation to Cancer With Roles Beyond Structural and Nutritional Support

Abstract

Stromal cells provide structural support and nutrients in secondary lymphoid organs and non-lymphoid tissues. However, accumulating evidence suggests that a complex relationship exists between stromal cells and immune cells. Interactions between immune cells and stromal cells have been shown to influence the pathology of both autoimmunity and cancer. This review examines the heterogeneity of stromal cells within the lymph node and non-lymphoid tissues during both homeostatic and inflammatory conditions, in particular autoimmunity and cancer, with the goal of better understanding the complex and apparently paradoxical relationship between these two classes of diseases. The review surveys potential novel mechanisms involving the interactions between stromal cells and immune cells which may contribute to the development, pathology and underlying connection between autoimmunity and cancer, including potential pathways from autoimmune inflammation to either “hot” or “cold” tumors. These interactions may provide some insights to explain the rising incidence of both autoimmunity and cancer in young women in industrialized countries and have the potential to be exploited in the development of new interventions for preventions and treatments of both autoimmune diseases and cancer.

Loss of T cell tolerance in the skin following immunopathology is linked to failed restoration of the dermal niche by recruited macrophages

“…The data presented herein imply that monocyte-derived macrophages that have been primed by the inflammatory aGVHD environment also have an on-going role in shaping the dermal environment beyond the primary disease, and that changes to the macrophage niche impact on third-party endogenous T cells, subsequent to the allogeneic response. Stromal cells within tissues, such as the liver, provide a niche within which macrophages differentiate ( Bonnardel et al., 2019 ), and adaptation of stromal cells to a chronically inflamed environment has been linked to local immune cell dysregulation and autoimmunity under conditions of chronic inflammation ( Honan and Chen, 2021 ). Analysis of secreted proteins in the dermis during aGVHD demonstrated upregulation of factors, such as PDGF-BB, which is a mitogenic factor for fibroblasts.…”

Lymph Node Stromal Cell–Intrinsic MHC Class II Expression Promotes MHC Class I–Restricted CD8 T Cell Lineage Conversion to Regulatory CD4 T Cells

“…Their functions are often affected by the geographical location of the cells. For example, various LEC populations can be found within the subcapsular and medullary sinus whereas the FRC population can be divided into subsets based on the T cell and B cell regions of the lymph node (74,75). It is possible that within the gut microenvironment yet-to-be-identified factors, such as microbial or other factors from intestinal drainage, may allow for site-specific functions of the LNSCs (76).…”

Lymphoid stromal cells - potential implications for the pathogenesis of CVID

“…In support of the reported role of stromal cells in tolerance maintenance or pathogenesis of autoimmunity (46,48,(53)(54)(55), LSCs are thought to be involved in the pathogenesis of rheumatoid arthritis (RA). Indeed, the lymph node stromal microenvironment displays alterations during the earliest phases of the disease.…”