Fish TNF and TNF receptors

Tumor necrosis factors(TNFs)are a group of cytokines that play critical roles in regulating a diverse range of physiological processes in vertebrates.TNFs function by activating a large number of structurally related receptors,leading to TNF mediated biological processes which are evolutionarily conserved.Fish have a much diversified TNF family,partly due to the whole genome duplication events which have occurred in this lineage,providing an excellent model to investigate the neo-and subfunctionalised properties of TNF superfamily.Fish possess most of the TNFs and receptors found in mammals and also some homologues exclusively present in fish.It seems that TNFSF4(OX40),TNFSF7(CD27)and TNFSF8(CD30)and their cognate receptors are absent in teleosts.It has been shown that fish viruses are able to produce TNFR homologues to establish infection by manipulating the host immune system.Understanding the roles of TNFSFs in fish immune defence and the pathogenesis of fish diseases will provide insights into the functions of TNFSFs from an evolutionary perspective and better strategies for improving fish health and welfare in aquaculture.This review summarises recent advances in the study of fish TNF biology and focuses on the molecular properties and immunological functions of the TNF and TNFR superfamily.

Acute heart failure as an adverse event of tumor necrosis factor inhibitor therapy in inflammatory bowel disease:A review of the literature

Tumor necrosis factor inhibitors(anti-TNFs)are widely used therapies for the treatment of inflammatory bowel diseases(IBD);however,their administration is not risk-free.Heart failure(HF),although rare,is a potential adverse event related to administration of these medications.However,the exact mechanism of development of HF remains obscure.TNFαis found in both healthy and damaged hearts.Its effects are concentration-and receptor-dependent,promoting either cardio-protection or cardiomyocyte apoptosis.Experimental rat models with TNFαreceptor knockout showed increased survival rates,less reactive oxygen species formation,and improved diastolic left ventricle pressure.However,clinical trials employing anti-TNF therapy to treat HF had disappointing results,suggesting abolishment of the cardioprotective properties of TNFα,making cardiomyocytes susceptible to apoptosis and oxidation.Thus,patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy.This review aims to discuss adverse events associated with the administration of anti-TNF therapy,with a focus on HF,and propose some approaches to avoid cardiac adverse events in patients with IBD.

Stimulation of TNF receptor type 2 expands regulatory T cells and ameliorates established collagen-induced arthritis in mice

Tumor necrosis factor(TNF)and its receptors TNF receptor type 1(TNFR1)and type 2(TNFR2)have a central role in chronic inflammatory diseases.While TNFR1 mainly confers inflammation,activation of TNFR2 elicits not only pro-inflammatory but also anti-inflammatory effects.In this study,we wanted to investigate the anti-inflammatory therapeutic potential of selective activation of TNFR2 in mice with established collageninduced arthritis.Mice with established arthritis induced by immunization with bovine collagen type II were treated with six injections of the TNFR2-specific agonist TNCscTNF80,given every second day.Two days after treatment cessation,the cell compositions of bone marrow,spleen and lymph nodes were analyzed.Mice were visually scored until day 30 after the start of therapy and the degree of joint inflammation was determined by histology.Treatment with TNCscTNF80 increased arthritis-induced myelopoiesis.Little effect was seen on the infiltration rate of inflammatory immature myeloid cells and on the reduction of lymphoid cells in secondary lymphoid organs.Upon treatment,frequency of regulatory T(Treg)cells in the CD4+T-cell population was increased in both spleen and inguinal lymph nodes.In addition,the expression of TNFR2 on Treg cells was enhanced.The clinical score started to improve 1 week after cessation treatment and remained lower 30 days after initiation of therapy.The histological score also revealed amelioration of joint inflammation in TNCscTNF80-treated versus control mice.Activation of TNFR2 might provide a suitable therapeutic strategy in autoimmune arthritis by increasing the numbers of regulatory cell types,in particular Treg cells,and by attenuation of arthritis.

LncRNA ZFPM2-AS1 promotes phyllodes tumor progression by binding to CDC42 and inhibiting STAT1 activation

Breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant behavior.Long non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involvement in breast PT remains largely unexplored.In this study,microarray was leveraged for the first time to investigate the role of lncRNA in PT.We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT,and its overexpression endowed PT with high tumor grade and adverse prognosis.Furthermore,we elucidated that ZFPM2-AS1 promotes the proliferation,migration,and invasion of malignant PT in vitro.Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft(PDX)model could effectively inhibit tumor progression in vivo.Mechanistically,our findings showed that ZFPM2-AS1 is competitively bound to CDC42,inhibiting ACK1 and STAT1 activation,thereby launching the transcription of TNFRSF19.In conclusion,our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT,and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.