title: 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, MHC-antigen 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.
authors.affiliation: Department of Immunemodulation at the Dermatology, University Hospital Erlangen, Erlangen, Germany. goldwias@me.com
authors.forename: Andreas
authors.initials: A
authors.lastname: Goldwich
authors.forename: Miriam
authors.initials: M
authors.lastname: Burkard
authors.forename: Martha
authors.initials: M
authors.lastname: Olke
authors.forename: Christoph
authors.initials: C
authors.lastname: Daniel
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Christian
authors.initials: C
authors.lastname: Hugo
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
authors.forename: Alexander
authors.initials: A
authors.lastname: Steinkasserer
authors.forename: André
authors.initials: A
authors.lastname: Gessner
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology / Q000473:pathology; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D005260:Female; D050533:Glomerular Basement Membrane / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D060730:Glomerular Filtration Barrier / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008863:Microspheres; D010047:Ovalbumin / Q000276:immunology / Q000493:pharmacokinetics; D010587:Phagocytosis / Q000276:immunology; D050199:Podocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D010047:Ovalbumin
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