Th1 and Th17 cells induce proliferative glomerulonephritis.
Th1 effector CD4+ cells contribute to the pathogenesis of proliferative and crescentic glomerulonephritis, but whether effector Th17 cells also contribute is unknown. We compared the involvement of Th1 and Th17 cells in a mouse model of antigen-specific glomerulonephritis in which effector CD4+ cells are the only components of adaptive immunity that induce injury. We planted the antigen ovalbumin on the glomerular basement membrane of Rag1(-/-) mice using an ovalbumin-conjugated non-nephritogenic IgG1 monoclonal antibody against alpha3(IV) collagen. Subsequent injection of either Th1- or Th17-polarized ovalbumin-specific CD4+ effector cells induced proliferative glomerulonephritis. Mice injected with Th1 cells developed progressive albuminuria over 21 d, histologic injury including 5.5 +/- 0.9% crescent formation/segmental necrosis, elevated urinary nitrate, and increased renal NOS2, CCL2, and CCL5 mRNA. Mice injected with Th17 cells developed albuminuria by 3 d; compared with Th1-injected mice, their glomeruli contained more neutrophils and greater expression of renal CXCL1 mRNA. In conclusion, Th1 and Th17 effector cells can induce glomerular injury. Understanding how these two subsets mediate proliferative forms of glomerulonephritis may lead to targeted therapies.
Summers
Shaun A
SA
Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia.
Steinmetz
Oliver M
OM
Li
Ming
M
Kausman
Joshua Y
JY
Semple
Timothy
T
Edgtton
Kristy L
KL
Borza
Dorin-Bogdan
DB
Braley
Hal
H
Holdsworth
Stephen R
SR
Kitching
A Richard
AR
D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D016654:Genes, RAG-1; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D018925:Chemokines; D007074:Immunoglobulin G; D020381:Interleukin-17; D012333:RNA, Messenger; D010047:Ovalbumin