microRNAs(miRNAs)are small noncoding RNAs that mediate RNA interference to suppress protein expression at the translational level.Accumulated evidence indicates that miRNAs play critical roles in various biological pr...microRNAs(miRNAs)are small noncoding RNAs that mediate RNA interference to suppress protein expression at the translational level.Accumulated evidence indicates that miRNAs play critical roles in various biological processes and disease development,including autoimmune diseases.Invariant natural killer T(iNKT)cells are an unusual CD1d-restricted subset of thymus-derived T cells that are potent regulators of diverse immune responses.Our previous studies with the mouse model of bone marrow-specific Dicer deletion suggest the involvement of Dicer-dependent miRNAs in the development and function of iNKT cells.In the present study,to further dissect the functional levels of Dicer-dependent miRNAs in regulating iNKT cell development,we generated a mouse model with the Dicer deletion in the thymus.Our data indicate that lack of miRNAs following the deletion of Dicer in the thymus severely interrupted the development and maturation of iNKT cells in the thymus and significantly decreased the number of iNKT cells in the peripheral immune organs.miRNA-deficient peripheral iNKT cells display profound defects in activation and cytokine production upon a-galactosylceramide(a-GalCer)stimulation.Our results demonstrate a critical role of the miRNA-dependent pathway in the thymus in the regulation of iNKT cell development and function.展开更多
Mucosal-associated invariant T(MAIT)cells are unconventional T cells that have been conserved throughout mammalian evolution,displaying innate and effector-like qualities[1,2].MAIT cells express a semi-invariant T-cel...Mucosal-associated invariant T(MAIT)cells are unconventional T cells that have been conserved throughout mammalian evolution,displaying innate and effector-like qualities[1,2].MAIT cells express a semi-invariant T-cell receptor,which recognizes vitamin B metabolites produced by various bacteria and yeast organisms,presented on the restriction molecule major histocompatibility complex(MHC)-related protein-1(MR1)[3].In mice,MAIT cells undergo three developmental stages in the thymus,giving rise to two subsets,MAIT1 and MAIT17,which secrete IFN-and IL-17 to combat infections[4,5].展开更多
Hidradenitis suppurativa(HS)is a chronic inflammatory skin disease with a worldwide prevalence of 0.3–4.0%,wherein abscesses and dermal sinus tracts form in intertriginous skin[1].HS remains poorly treated due to a l...Hidradenitis suppurativa(HS)is a chronic inflammatory skin disease with a worldwide prevalence of 0.3–4.0%,wherein abscesses and dermal sinus tracts form in intertriginous skin[1].HS remains poorly treated due to a lack of knowledge regarding its immunopathogenesis[2].展开更多
Mucosal-associated invariant T(MAIT)cells are an evolutionarily conserved subset of T cells that respond to microbial threats via semi-invariant T cell receptor(TCR)-mediated recognition of microbial riboflavin-deriva...Mucosal-associated invariant T(MAIT)cells are an evolutionarily conserved subset of T cells that respond to microbial threats via semi-invariant T cell receptor(TCR)-mediated recognition of microbial riboflavin-derivative antigens presented by MHC class I-related(MR1)molecules[1].MAIT cells mediate functions that link innate and acquired immunity in a broad spectrum of diseases,including infection,cancer,allergy,and autoimmunity[2].MAIT cells are abundant in human nonmucosal tissues,where they account for up to 10%of blood T cells and 45%of liver T cells,but are much less abundant in mice[3].展开更多
基金by grants from Juvenile Diabetes Research Foundation International(1-2005-1039,5-2006-688 and 5-2006-918)American Diabetes Association(7-05-JF-30).
文摘microRNAs(miRNAs)are small noncoding RNAs that mediate RNA interference to suppress protein expression at the translational level.Accumulated evidence indicates that miRNAs play critical roles in various biological processes and disease development,including autoimmune diseases.Invariant natural killer T(iNKT)cells are an unusual CD1d-restricted subset of thymus-derived T cells that are potent regulators of diverse immune responses.Our previous studies with the mouse model of bone marrow-specific Dicer deletion suggest the involvement of Dicer-dependent miRNAs in the development and function of iNKT cells.In the present study,to further dissect the functional levels of Dicer-dependent miRNAs in regulating iNKT cell development,we generated a mouse model with the Dicer deletion in the thymus.Our data indicate that lack of miRNAs following the deletion of Dicer in the thymus severely interrupted the development and maturation of iNKT cells in the thymus and significantly decreased the number of iNKT cells in the peripheral immune organs.miRNA-deficient peripheral iNKT cells display profound defects in activation and cytokine production upon a-galactosylceramide(a-GalCer)stimulation.Our results demonstrate a critical role of the miRNA-dependent pathway in the thymus in the regulation of iNKT cell development and function.
基金NIH RO1Al119041(QSM)Henry Ford Immunology Program grants(T71016,QSM+1 种基金T71017,LZ)the Henry Ford Cancer Institute Postdoctoral fellowship program(JW and KS).
文摘Mucosal-associated invariant T(MAIT)cells are unconventional T cells that have been conserved throughout mammalian evolution,displaying innate and effector-like qualities[1,2].MAIT cells express a semi-invariant T-cell receptor,which recognizes vitamin B metabolites produced by various bacteria and yeast organisms,presented on the restriction molecule major histocompatibility complex(MHC)-related protein-1(MR1)[3].In mice,MAIT cells undergo three developmental stages in the thymus,giving rise to two subsets,MAIT1 and MAIT17,which secrete IFN-and IL-17 to combat infections[4,5].
基金funded by NIH/NIAMS(R01AR078688 to Q-SM and WL,R21AR079089 to Q-SM and IA)the Henry Ford Immunology Program(T71016 to Q-SM and T71017 to LZ).
文摘Hidradenitis suppurativa(HS)is a chronic inflammatory skin disease with a worldwide prevalence of 0.3–4.0%,wherein abscesses and dermal sinus tracts form in intertriginous skin[1].HS remains poorly treated due to a lack of knowledge regarding its immunopathogenesis[2].
基金Henry Ford Immunology Research Program(T71016 to QSM,T71017 to LZ).
文摘Mucosal-associated invariant T(MAIT)cells are an evolutionarily conserved subset of T cells that respond to microbial threats via semi-invariant T cell receptor(TCR)-mediated recognition of microbial riboflavin-derivative antigens presented by MHC class I-related(MR1)molecules[1].MAIT cells mediate functions that link innate and acquired immunity in a broad spectrum of diseases,including infection,cancer,allergy,and autoimmunity[2].MAIT cells are abundant in human nonmucosal tissues,where they account for up to 10%of blood T cells and 45%of liver T cells,but are much less abundant in mice[3].