| First Author | Hünemörder S | Year | 2015 |
| Journal | J Pathol | Volume | 237 |
| Issue | 1 | Pages | 62-71 |
| PubMed ID | 25965582 | Mgi Jnum | J:225614 |
| Mgi Id | MGI:5693707 | Doi | 10.1002/path.4559 |
| Citation | Hunemorder S, et al. (2015) TH1 and TH17 cells promote crescent formation in experimental autoimmune glomerulonephritis. J Pathol 237(1):62-71 |
| abstractText | Autoimmunity against the Goodpasture antigen alpha3IV-NC1 results in crescentic glomerulonephritis (GN). Both antibodies and T cells directed against alpha3IV-NC1 have been implicated in disease development and progression. Using the model of experimental autoimmune glomerulonephritis (EAG) in DBA/1 mice, we aimed to characterize the frequency and function of alpha3IV-NC1-specific CD4(+) T cells in the kidneys. DBA/1 mice repeatedly immunized with human alpha3IV-NC1 developed necrotizing/crescentic GN. Kidneys with crescentic GN contained CD4(+) cells responding to alpha3IV-NC1 with the production of IFN-gamma or IL-17A, demonstrating the accumulation of both alpha3IV-NC1-specific TH1 and TH17 cells. To test the functional relevance of TH1 and TH17 cells, EAG was induced in DBA/1 mice deficient in IFN-gammaR, IL-17A or IL-23p19. Mice of all knockout groups mounted alpha3IV-NC1 IgG, developed nephrotic range proteinuria, and IgG deposition to the glomerular basement membranes at levels similar to immunized wild-type mice. However, all knockout groups showed significantly fewer glomerular crescents and attenuated tubulointerstitial damage. Our results suggest that both alpha3IV-NC1-specific TH1 and TH17 cells accumulate in the kidneys and are crucial for the development of necrotizing/crescentic GN. |
