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Objective To figure out the functions of thymic stromal lymphopoietin (TSLP) in IgG4-related disease (IgG4-RD). Methods Plasma TSLP levels were tested by Elisa, and its receptors were detected by flow cytometry. Expressions of TSLP and TSLPR in involved tissues were stained by immunohistochemistry and immunofluorescence. Proliferation, apoptosis, and B subsets of TSLP stimulated-B cells were analyzed by flow cytometry. TSLP-stimulated B cells were co-cultured with CD4+ Naïve T cells. Signaling pathway was identified by RNA-sequencing and western blot. Anti-TSLP therapy was adapted in LatY136F knock-in mice (Lat, IgG4-RD mouse model). Results Plasma TSLP level was increased in IgG4-RD patients and was positively correlated with serum IgG4 level and responder index (RI). TSLPR was co-localized with CD19+ B cells in the submandibular glands (SMGs) of IgG4-RD. TSLP promoted B cell proliferation, and TSLP-activated B cells polarized CD4+ naive T cells into follicular helper T (Tfh) cells through OX40L. RNA-sequencing identified JAK-STAT signaling pathway in TSLP-activated B cells and it was verified by western blot. Anti-TSLP therapy alleviated the inflammation of lung in Lat mice. Conclusion Elevated TSLP in IgG4-RD promoted B cells proliferation and polarized Tfh cells and might be served as a potential therapeutic target.

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease with high heterogeneity but the common characterization of numerous autoantibodies and systemic inflammation which lead to the damage of multiple organs. Aberrance of B cells plays a pivotal role in the immunopathogenesis of SLE via both antibody-dependent and antibody-independent manners. Escape of autoreactive B cells from the central and peripheral tolerance checkpoints, over-activation of B cells and their excessive cytokines release which drive T cells and dendritic cells stimulation, and dysregulated surface molecules, as well as intracellular signal pathways involved in B cell biology, are all contributing to B cell aberrance and participating in the pathogenesis of SLE. Based on that rationale, targeting aberrance of B cells and relevant molecules and pathways is expected to be a promising strategy for lupus control. Multiple approaches targeting B cells through different mechanisms have been attempted, including B-cell depletion via monoclonal antibodies against B-cell-specific molecules, blockade of B-cell survival and activation factors, suppressing T-B crosstalk by interrupting costimulatory molecules and inhibiting intracellular activation signaling cascade by targeting pathway molecules in B cells. Though most attempts ended in failure, the efficacy of B-cell targeting has been encouraged by the FDA approval of belimumab that blocks B cell-activating factor (BAFF) and the recommended use of anti-CD20 as a remedial therapy in refractory lupus. Still, quantities of clinical trials targeting B cells or relevant molecules are ongoing and some of them have displayed promising preliminary results. Additionally, advances in multi-omics studies help deepen our understandings of B cell biology in lupus and may promote the discovery of novel potential therapeutic targets. The combination of real-world data with basic research achievements may pave the road to conquering lupus.

Background Choledocholithiasis is an endemic condition in the world. Although rare, foreign body migration with biliary complications needs to be considered in the differential diagnosis for patients presenting with typical symptoms even many years after cholecystectomy, EPCP, war-wound, foreign body ingestion or any other particular history before. It is of great clinical value as the present review may offer some help when dealing with choledocholithiasis caused by foreign bodies. Case presentation We reported a case of choledocholithiasis caused by fishbone from choledochoduodenal anastomosis regurgitation. Moreover, we showed up all the instances of choledocholithiasis caused by foreign bodies published until June 2018 and wrote the world’s first literature review of foreign bodies in the bile duct of 144 cases. The findings from this case suggest that the migration of fishbone can cause various consequences, one of these, as we reported here, is as a core of gallstone and a cause of choledocholithiasis. Conclusion The literature review declared the choledocholithiasis caused by foreign bodies prefer the wrinkly and mainly comes from three parts: postoperative complications, foreign body ingestion, and post-war complications such as bullet injury and shrapnel wound. The Jonckheere-Terpstra test indicated the ERCP was currently the treatment of choice. It is a very singular case of choledocholithiasis caused by fishbone, and the present review is the first one concerning choledocholithiasis caused by foreign bodies all over the world.