Naive CD4 T cells can differentiate into at least two different types ofT helpers, Thl and Th2 cells. Th2 cells, capable of producing IL-4, IL-5 and IL-13, are involved in humoral immunity against extracellular pathog...Naive CD4 T cells can differentiate into at least two different types ofT helpers, Thl and Th2 cells. Th2 cells, capable of producing IL-4, IL-5 and IL-13, are involved in humoral immunity against extracellular pathogens and in the induction of asthma and other allergic diseases. In this review, we summarize recent reports regarding the transcription factors involved in Th2 differentiation and cell expansion, including StatS, Gfi- 1 and GATA-3. Stats activation is necessary and sufficient for IL-2-mediated function in Th2 differentiation. Enhanced Stats signaling induces Th2 differentiation independent of IL-4 signaling; although it does not up-regulate GATA-3 expression, it does require the presence of GATA-3 for its action. Gfi-1, induced by IL-4, promotes the expansion of GATA-3-expressing cells. Analysis of conditional Gata3 knockout mice confirmed the critical role of GATA-3 in Th2 cell differentiation (both IL-4 dependent and IL-4 independent) and in Th2 cell proliferation and also showed the importance of basal GATA-3 expression in inhibiting Thl differentiation.展开更多
The type 2 immune response is critical for host defense against large parasites such as helminths.On the other hand,dysregulation of the type 2 immune response may cause immunopathological conditions,including asthma,...The type 2 immune response is critical for host defense against large parasites such as helminths.On the other hand,dysregulation of the type 2 immune response may cause immunopathological conditions,including asthma,atopic dermatitis,rhinitis,and anaphylaxis.Thus,a balanced type 2 immune response must be achieved to mount effective protection against invading pathogens while avoiding immunopathology.The classical model of type 2 immunity mainly involves the differentiation of type 2 T helper(Th2)cells and the production of distinct type 2 cytokines,including interleukin-4(IL-4),IL-5,and IL-13.Group 2 innate lymphoid cells(ILC2s)were recently recognized as another important source of type 2 cytokines.Although eosinophils,mast cells,and basophils can also express type 2 cytokines and participate in type 2 immune responses to various degrees,the production of type 2 cytokines by the lymphoid lineages,Th2 cells,and ILC2s in particular is the central event during the type 2 immune response.In this review,we discuss recent advances in our understanding of how ILC2s and Th2 cells orchestrate type 2 immune responses through direct and indirect interactions.展开更多
Toll-like receptors (TLR) are pathogen-associated molecular patterns (PAMPs) recognition receptors that play an important role in protective immunity against infection and inflammation.They act as central integrators ...Toll-like receptors (TLR) are pathogen-associated molecular patterns (PAMPs) recognition receptors that play an important role in protective immunity against infection and inflammation.They act as central integrators of a wide variety of signals,responding to diverse agonists of microbial products.Stimulation of Toll-like receptors by microbial products leads to signaling pathways that activate not only innate,but also adaptive immunity by APC dependent or independent mechanisms.Recent evidence revealed that TLR signals played a determining role in the skewing of na(?)ve T cells towards either Th1 or Th2 responses.Activation of Toll-like receptors also directly or indirectly influences regulatory T cell functions.Therefore,TLRs are required in both immune activation and immune regulation.Study of TLRs has significantly enhanced our understanding of innate and adaptive immune responses and provides novel therapeutic approaches against infectious and inflammatory diseases.Cellular & Molecular Immunology.2004;1(4):239-246.展开更多
文摘Naive CD4 T cells can differentiate into at least two different types ofT helpers, Thl and Th2 cells. Th2 cells, capable of producing IL-4, IL-5 and IL-13, are involved in humoral immunity against extracellular pathogens and in the induction of asthma and other allergic diseases. In this review, we summarize recent reports regarding the transcription factors involved in Th2 differentiation and cell expansion, including StatS, Gfi- 1 and GATA-3. Stats activation is necessary and sufficient for IL-2-mediated function in Th2 differentiation. Enhanced Stats signaling induces Th2 differentiation independent of IL-4 signaling; although it does not up-regulate GATA-3 expression, it does require the presence of GATA-3 for its action. Gfi-1, induced by IL-4, promotes the expansion of GATA-3-expressing cells. Analysis of conditional Gata3 knockout mice confirmed the critical role of GATA-3 in Th2 cell differentiation (both IL-4 dependent and IL-4 independent) and in Th2 cell proliferation and also showed the importance of basal GATA-3 expression in inhibiting Thl differentiation.
基金by the Division of Intramural Research of NIAID(US National Institutes of Health).
文摘The type 2 immune response is critical for host defense against large parasites such as helminths.On the other hand,dysregulation of the type 2 immune response may cause immunopathological conditions,including asthma,atopic dermatitis,rhinitis,and anaphylaxis.Thus,a balanced type 2 immune response must be achieved to mount effective protection against invading pathogens while avoiding immunopathology.The classical model of type 2 immunity mainly involves the differentiation of type 2 T helper(Th2)cells and the production of distinct type 2 cytokines,including interleukin-4(IL-4),IL-5,and IL-13.Group 2 innate lymphoid cells(ILC2s)were recently recognized as another important source of type 2 cytokines.Although eosinophils,mast cells,and basophils can also express type 2 cytokines and participate in type 2 immune responses to various degrees,the production of type 2 cytokines by the lymphoid lineages,Th2 cells,and ILC2s in particular is the central event during the type 2 immune response.In this review,we discuss recent advances in our understanding of how ILC2s and Th2 cells orchestrate type 2 immune responses through direct and indirect interactions.
文摘Toll-like receptors (TLR) are pathogen-associated molecular patterns (PAMPs) recognition receptors that play an important role in protective immunity against infection and inflammation.They act as central integrators of a wide variety of signals,responding to diverse agonists of microbial products.Stimulation of Toll-like receptors by microbial products leads to signaling pathways that activate not only innate,but also adaptive immunity by APC dependent or independent mechanisms.Recent evidence revealed that TLR signals played a determining role in the skewing of na(?)ve T cells towards either Th1 or Th2 responses.Activation of Toll-like receptors also directly or indirectly influences regulatory T cell functions.Therefore,TLRs are required in both immune activation and immune regulation.Study of TLRs has significantly enhanced our understanding of innate and adaptive immune responses and provides novel therapeutic approaches against infectious and inflammatory diseases.Cellular & Molecular Immunology.2004;1(4):239-246.