title: Pathway of Toll-like receptor 7/B cell activating factor/B cell activating factor receptor plays a role in immune thrombocytopenia in vivo.
abstract: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by anti-platelet autoantibody-mediated platelet destruction. Antigen-presenting cell (APC) dysfunction is considered to play crucial roles in ITP. However, how APC affects autoreactive B cells in ITP is still unknown. Using a mouse model of immune thrombocytopenia, we demonstrated an increase in levels of TLR7 in splenic mononuclear cells (SMCs). Using both TLR7 agonist and TLR7 silencing lentivirus, we found stimulation of TLR7 decreased platelet counts and increased levels of platelet-associated IgG (PAIgG) in ITP mice, which correlates TLR7 with platelet destruction by autoantibodies. Levels of serum BAFF increased significantly in ITP mice and stimulation of TLR7 promoted secretion of BAFF. Among the three BAFF receptors, only BAFF receptor (BAFF-R) increased in ITP mice. However, activation of TLR7 showed no effect on the expression of BAFF receptors. These findings indicate that upregulation of TLR7 may augment BAFF secretion by APC and through ligation of BAFF-R promote autoreactive B cell survival and thus anti-platelet autoantibody production. The pathway of TLR7/BAFF/BAFF-R provides us with an explanation of how activation of APC affects autoantibody production by B cells in ITP and thus might provide a reasonable therapeutic strategy for ITP.
authors.affiliation: Department of Parasitology, Shandong University School of Medicine, Jinan, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Shuqian
authors.initials: S
authors.lastname: Xu
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Xuping
authors.initials: X
authors.lastname: Wang
authors.forename: Daoxin
authors.initials: D
authors.lastname: Ma
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.forename: Ming
authors.initials: M
authors.lastname: Hou
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D020868:Gene Silencing; D007074:Immunoglobulin G / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D010976:Platelet Count; D015398:Signal Transduction / Q000276:immunology*; D013921:Thrombocytopenia / Q000097:blood / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000378:metabolism*
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; C505720:Tnfsf13b protein, mouse; D051199:Toll-Like Receptor 7