Flagellar filament structural protein induces Sjögren's syndrome‐like sialadenitis in mice

Abstract

Our data suggest that FliC-treated mice develop an SS-like phenotype. Our model may elucidate the relationship between commensal bacteria and SS.

RETRACTED ARTICLE: Effects of CREB1 gene silencing on cognitive dysfunction by mediating PKA-CREB signaling pathway in mice with vascular dementia

“…The rats were granted free access to food and water, placed on a 12 h light-dark cycle, with relative humidity conditions of 40% ~ 70% and noise levels < 50 dB. Ten mice were then randomly selected as the normal group, while the other 70 mice were used in order to establish the VD mouse model (Higuchi et al, 2017 ). The VD mouse model was established based on the following procedure: bilateral carotid artery ischemia reperfusion combined with tail bleeding, anesthetized by means of intraperitoneal injection with 40 mg/kg 0.4% pentobarbital sodium solution, and immobilized on an operating table followed by routine sterilization, and routine disinfection.…”

Outer Membrane Protein of Gut Commensal Microorganism Induces Autoantibody Production and Extra-Intestinal Gland Inflammation in Mice

“…It may be possible that the molecules did not possess the combined functionality of immunogenic antigens and bystander adjuvants [ 37 ], which are indispensable for autoimmunity [ 38 ]. In addition to the microbial molecules investigated in the present study, we previously studied the flagellar filament structural protein FliC, a TLR5-ligand, and an NLR apoptosis inhibitory protein (NAIP) activator, derived from commensal E. coli , which was repeatedly inoculated following the same regimen of injection as the present study [ 17 , 39 ]. In the reports, we had found that sialadenitis and pancreatitis could be induced by FliC in mice within the fifteen weeks of observation after the final inoculation [ 17 , 39 ].…”

“…In addition to the microbial molecules investigated in the present study, we previously studied the flagellar filament structural protein FliC, a TLR5-ligand, and an NLR apoptosis inhibitory protein (NAIP) activator, derived from commensal E. coli , which was repeatedly inoculated following the same regimen of injection as the present study [ 17 , 39 ]. In the reports, we had found that sialadenitis and pancreatitis could be induced by FliC in mice within the fifteen weeks of observation after the final inoculation [ 17 , 39 ]. The results of the present study indicated that OmpA was highly antigenic to induce humoral adaptive immune response to elicit antibodies and to encounter histological inflammation of the Harderian and the salivary glands, but not of the pancreas, indicating that different microbe-derived proteins had initiated inflammation in exocrine glands with tropism.…”

“…Salmonella OmpA induces expression of MHC class II and co-stimulatory molecules on DCs in mice [ 42 ] and differentiate naïve CD4 + T cell biased towards Th1 and Th17 [ 42 , 43 , 44 , 45 ]. In our mouse model, IL-1β, IFN-γ, and IL-17A were inflammatory cytokines that were predominantly produced in sera, similar to the cytokine production by FliC [ 17 ]. In addition to cytokine production, OmpA of Klebsiella pneumoniae after endocytosis by DCs has been shown to gain access to the cytosolic MHC class I presentation pathway to elicit cytotoxic T cells (CTLs), in the absence of CD4 + T cell help or adjuvant.…”

“…Dysbiosis of increased facultative anaerobes exceeds commensal tolerance and stimulates innate immune activation beyond the intestinal niche [ 14 ], such as atherosclerosis [ 14 , 15 ]. Several of the bacterial components have been implicated in the development of autoimmunity, including the microbial-von Willebrand factor type A domain protein (vWFA) [ 16 ] and the flagellin FliC [ 17 ] in sialoadenitis of Sjögren’s syndrome (SS), and the outer membrane protein OmpC in the synovial membrane of rheumatoid arthritis [ 18 ].…”