The autoimmune regulator(AIRE)is a crucial factor for the induction of central tolerance,and mutations in this gene lead to abnormal immune responses.However,the role of AIRE in autophagy in immune cells,especially in...The autoimmune regulator(AIRE)is a crucial factor for the induction of central tolerance,and mutations in this gene lead to abnormal immune responses.However,the role of AIRE in autophagy in immune cells,especially in monocytes,is obscure.In the present study,we found that overexpression of AIRE in THP-1 human monocytes resulted in increased endogenous light chain 3(LC3)-II level and elevated LC3 positive vesicles.Moreover,an autophagy inhibitor or knockdown of AIRE by small interference RNA attenuated these effects.In contrast,the expression of p62/SQSTM1 remained unchanged in THP-1 cells after the corresponding treatment.Our findings indicate that AIRE plays a role in the regulation of autophagy in THP-1 human monocytes.展开更多
Selenium （Se） is an essential trace element. Autoimmune thyroid diseases （AITD） are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the ...Selenium （Se） is an essential trace element. Autoimmune thyroid diseases （AITD） are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the effects of Se on the cytokines in AITD are still unclear. So we researched the role of Selenium （Se） and Thl/Th2 cytokine productions in the pathogenesis of autoimmune thyroid diseases （AITD）.展开更多
Objective To investigate the effets of nordihydroguaiaretic acid(NDGA)on the expression of IL-6,IL-17and TGF-βin mice with experimental autoimmune encephalomyelitis(EAE).Methods C57BL/6 mice were immunized with MOG35...Objective To investigate the effets of nordihydroguaiaretic acid(NDGA)on the expression of IL-6,IL-17and TGF-βin mice with experimental autoimmune encephalomyelitis(EAE).Methods C57BL/6 mice were immunized with MOG35-55 to induce EAE.The 54 mice were randomly and equally divided into control group,model group and treatment group.Mice in treatment展开更多
The expression of self-antigens in medullary thymic epithelial cells(mTECs)is essential for the establishment of immune tolerance,but the regulatory network that controls the generation and maintenance of the multitud...The expression of self-antigens in medullary thymic epithelial cells(mTECs)is essential for the establishment of immune tolerance,but the regulatory network that controls the generation and maintenance of the multitude of cell populations expressing self-antigens is poorly understood.Here,we show that Insm1,a zinc finger protein with known functions in neuroendocrine and neuronal cells,is broadly coexpressed with an autoimmune regulator(Aire)in mTECs.Insm1 expression is undetectable in most mimetic cell populations derived from mTECs but persists in neuroendocrine mimetic cells.Mutation of Insm1 in mice downregulated Aire expression,dysregulated the gene expression program of mTECs,and altered mTEC subpopulations and the expression of tissue-restricted antigens.Consistent with these findings,loss of Insm1 resulted in autoimmune responses in multiple peripheral tissues.We found that Insm1 regulates gene expression in mTECs by binding to chromatin.Interestingly,the majority of the Insm1 binding sites are co-occupied by Aire and enriched in superenhancer regions.Together,our data demonstrate the important role of Insm1 in the regulation of the repertoire of self-antigens needed to establish immune tolerance.展开更多
文摘The autoimmune regulator(AIRE)is a crucial factor for the induction of central tolerance,and mutations in this gene lead to abnormal immune responses.However,the role of AIRE in autophagy in immune cells,especially in monocytes,is obscure.In the present study,we found that overexpression of AIRE in THP-1 human monocytes resulted in increased endogenous light chain 3(LC3)-II level and elevated LC3 positive vesicles.Moreover,an autophagy inhibitor or knockdown of AIRE by small interference RNA attenuated these effects.In contrast,the expression of p62/SQSTM1 remained unchanged in THP-1 cells after the corresponding treatment.Our findings indicate that AIRE plays a role in the regulation of autophagy in THP-1 human monocytes.
基金supported by three programs from the National Natural Science Foundation of China (NSFC) (The experimental study on the effect of trace elements iodine and selenium on the autoimmune thyroid disease (No.30571564)The cross-sectional investigation on hypothyroidism induced by excess iodine intake and the experimental research on pathogenesy (No.30972465)The change of thyroid pathology and the levels of T3,T4 in SePP1,GPX3 knock out mice (No.30810103004)
文摘Selenium （Se） is an essential trace element. Autoimmune thyroid diseases （AITD） are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the effects of Se on the cytokines in AITD are still unclear. So we researched the role of Selenium （Se） and Thl/Th2 cytokine productions in the pathogenesis of autoimmune thyroid diseases （AITD）.
文摘Objective To investigate the effets of nordihydroguaiaretic acid(NDGA)on the expression of IL-6,IL-17and TGF-βin mice with experimental autoimmune encephalomyelitis(EAE).Methods C57BL/6 mice were immunized with MOG35-55 to induce EAE.The 54 mice were randomly and equally divided into control group,model group and treatment group.Mice in treatment
基金supported by the National Natural Science Foundation of China(31970856)the Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University(JNU1AF-CFTP-2022-a01236)the Science and Technology Program of Guangzhou(202201020042).
文摘The expression of self-antigens in medullary thymic epithelial cells(mTECs)is essential for the establishment of immune tolerance,but the regulatory network that controls the generation and maintenance of the multitude of cell populations expressing self-antigens is poorly understood.Here,we show that Insm1,a zinc finger protein with known functions in neuroendocrine and neuronal cells,is broadly coexpressed with an autoimmune regulator(Aire)in mTECs.Insm1 expression is undetectable in most mimetic cell populations derived from mTECs but persists in neuroendocrine mimetic cells.Mutation of Insm1 in mice downregulated Aire expression,dysregulated the gene expression program of mTECs,and altered mTEC subpopulations and the expression of tissue-restricted antigens.Consistent with these findings,loss of Insm1 resulted in autoimmune responses in multiple peripheral tissues.We found that Insm1 regulates gene expression in mTECs by binding to chromatin.Interestingly,the majority of the Insm1 binding sites are co-occupied by Aire and enriched in superenhancer regions.Together,our data demonstrate the important role of Insm1 in the regulation of the repertoire of self-antigens needed to establish immune tolerance.
