Podocytes Are Nonhematopoietic Professional Antigen-Presenting Cells

Abstract

Podocytes are essential to the structure and function of the glomerular filtration barrier; however, they also exhibit increased expression of MHC class II molecules under inflammatory conditions, and they remove Ig and immune complexes from the glomerular basement membrane (GBM). This finding suggests that podocytes may act as antigen-presenting cells, taking up and processing antigens to initiate specific T cell responses, similar to professional hematopoietic cells such as dendritic cells or macrophages. Here, MHCantigen complexes expressed exclusively on podocytes of transgenic mice were sufficient to activate CD8+ T cells in vivo. In addition, deleting MHC class II exclusively on podocytes prevented the induction of experimental anti-GBM nephritis. Podocytes ingested soluble and particulate antigens, activated CD4+ T cells, and crosspresented exogenous antigen on MHC class I molecules to CD8+ T cells. In conclusion, podocytes participate in the antigen-specific activation of adaptive immune responses, providing a potential target for immunotherapies of inflammatory kidney diseases and transplant rejection.

T cell infiltration is associated with kidney injury in patients with anti-glomerular basement membrane disease

“…Other resident glomerular cells may have more significant roles in the activation of T cells around the glomeruli. Recent studies have indicated that podocytes from parietal epithelial cells were the predominant cellular components of crescents (Appel et al, 2009); these podocytes function as local professional antigen-presenting cells in the kidney (Goldwich et al, 2013) and may destroy its structure (Li et al, 2015). Further studies are required to determine the mechanisms of interaction between T cells and podocytes to elucidate the activation of CD4 + cells in the kidney in situ.…”

Inflammasomes in the Pathophysiology of Kidney Diseases

“…Zhang et al [21] further showed that murine podocytes expressed NLRP3, ASC and caspase-1, and in mice with hyperhomocysteinemia, IL-1β increased in the glomeruli. Given that podocytes act like dendritic cells and infiltrating macrophages [22], their ability to participate in inflammation is convincing. Whether these controversial results are the result of different stimuli remains unknown.…”

Transplant Glomerulopathy

“…Podocytes express MHC class I and class II molecules, and this increases under inflammatory conditions. 11,12 Furthermore, podocytes can serve as antigen-presenting cells, and deleting MHC class II exclusively on podocytes markedly attenuates the severity of GN in a mouse model of anti-GBM nephritis. 12 Yang et al 9 did not compare glomerulitis in their cases of early versus late TG, and they observed acute ABMR only infrequently before the development of early or late TG, although diagnosis was based on an older version of the Banff classification that did not recognize C4d-negative ABMR.…”

“…11,12 Furthermore, podocytes can serve as antigen-presenting cells, and deleting MHC class II exclusively on podocytes markedly attenuates the severity of GN in a mouse model of anti-GBM nephritis. 12 Yang et al 9 did not compare glomerulitis in their cases of early versus late TG, and they observed acute ABMR only infrequently before the development of early or late TG, although diagnosis was based on an older version of the Banff classification that did not recognize C4d-negative ABMR. However, 5 of 8 cases of early TG were associated with a history of TCMR (Banff 1A or above) compared with only 2 of 17 cases of late TG, suggesting that an inflammatory environment may have been present, at least transiently, in the majority of kidneys developing early TG, 6 of 8 of which were also exposed to DSAs.…”