title: Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis.
abstract: BACKGROUND
  Immunoglobulin class-switch recombination (CSR) is crucial for the expression of IgA, and it plays a vital role in the physiopathology of IgA nephropathy (IgAN). The aim of the study is to investigate the effect of polyriboinosinic:polyribocytidylic acid (poly(I:C)) in modulating toll-like receptor (TLR) 3-B-cell-activating factor belonging to the TNF family (BAFF) axis activation, which in turn promotes IgA CSR of IgAN patients and the IgAN rat model.
  
  
  METHODS
  Blood samples and tonsillar tissue specimens were obtained from 24 patients with IgAN and 26 patients with chronic tonsillitis as control. We also used the IgAN rat model to investigate the relationship between viral infection and IgA CSR.
  
  
  RESULTS
  Immunohistochemical and ELISA western blotting examination revealed that the TLR3/BAFF axis is activated in IgAN patients when compared to controls. Synthetic double-stranded RNA poly(I:C) stimulation upregulates the TACI/TLR3/TRIF/TRAF6 expression and promotes IgA CSR and BAFF productions in tonsil mononuclear cells. TLR3 or BAFF siRNA decreases IgA expression. In IgAN rat models, TLR3/BAFF signaling was highly activated. With 200 μg poly(I:C) sodium salt into the left naris for 8 weeks, IgA was highly deposited on glomeruli. It also revealed that poly(I:C) activated TLR3/BAFF axis and IgA CSR in vivo.
  
  
  CONCLUSIONS
  These data points toward the role of TLR3/BAFF axis in IgA CSR of IgAN, and the data also support the notion that mucosal immunization with virus infection results in impaired mucosal and systemic IgA responses.
authors.affiliation: Nephrology Department, The Second Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan, Changsha, Hunan, People's Republic of China.
authors.forename: Liyu
authors.initials: L
authors.lastname: He
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Peng
authors.forename: Jiayi
authors.initials: J
authors.lastname: Wang
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Tang
authors.forename: Xun
authors.initials: X
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Fuyou
authors.initials: F
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.forename: Youming
authors.initials: Y
authors.lastname: Peng
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D053264:B-Cell Activating Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A; D017578:Immunoglobulin Class Switching; D008297:Male; D008875:Middle Aged; D014066:Palatine Tonsil / Q000378:metabolism; D011070:Poly I-C; D011119:Polynucleotides / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D053264:B-Cell Activating Factor; D007070:Immunoglobulin A; D011119:Polynucleotides; C495344:TLR3 protein, human; C530472:TLR3 protein, rat; C505719:TNFSF13B protein, human; D051196:Toll-Like Receptor 3; D011070:Poly I-C