Cytokines IV.PDF

See online version for abbreviations and references.1062 Cell 132,March 21,2008 2008 Elsevier Inc.DOI 10.1016/j.cell.2008.02.024SnapShot:Cytokines IVCristina M.Tato and Daniel J.CuaSchering-Plough Biopharma(Formerly DNAX Research),Palo Alto,CA 94304,USACytokine Receptor SourceTargetsMajor FunctionDisease AssociationFLT3 LigandReceptor tyrosine kinasesDiverse tissueDCs,other myeloid cellsDifferentiation and proliferation;synergizes with stem cell factor=impaired hematopoietic stem cell repopulation and B cell precursorsG-CSFGCSFR dimerMacrophages,fibroblasts,other tissuesCommitted progenitorsDifferentiation and activation of granulocytes=neutropenia GM-CSFGM-CSFR,cT cells,macrophages,fibroblasts,othersMacrophages,granulocytes,dendritic cells,and progenitorsInflammatory;induction of activation;differ-entiation,growth,and survival=affects alveolar functionIFN/IFNR1,IFNR2Macrophages,fibroblasts,plasmacytoid DCs,othersNK cells,many othersPromotes resistance to viral pathogens;promotes increased expression of MHC class I=impaired antiviral responsesIFNIFNR1,IFNR2Th1 cells,NK cells,CD8 T cellsMacrophages,NK cells,T cells,othersPromotes activation of APCs and cell-mediated immunity;increased MHC class II expression=susceptibility to intracellular pathogensLIFLIFR,gp130Macrophages,T cells,fibroblasts,uterus,othersEmbryonic stem cells,hematopoietic cells,othersCell survival=deficient hematopoietic progenitor cells;defective blastocyst implantationM-CSFReceptor tyrosine kinasesMonocytes,fibroblasts,othersCommitted myeloid progenitorsDifferentiation;prolifera-tion and survival=monocyte deficiency;osteopetrosisMIFCD74 trimer,CD44Macrophages,T cellsMacrophagesCell migration,DTH response =susceptibility to Gram-negative bacteriaOSMLIFR or OSM-R,gp130Macrophages,fibroblasts,othersMyeloid cells,embryonic stem cells,T cells,othersDifferentiation;induction of immune response(early)Stem Cell FactorReceptor tyrosine kinasesBone marrowStem cells,mast cellsActivation and growth=impaired hematopoietic stem cell proliferation and melanocyte productionTGF 1,2,3TGFR type I,type II,and type IIIT cells,DCs,macrophages,othersAll leukocyte populationsRegulatory;inhibits growth and activation;Treg maintenance;synergizes with IL-6 to promote Th17=increased susceptibility to autoimmune disorders =fibrotic diseasesTSLP LigandTSLPR,IL7RSkin,lung,and gutDCs and other myeloid cellsPromotes Th2 develop-ment(human);B cell development(mouse)=atopic diseasesSnapShot:Cytokines I-IVCytokines I highlights the first 16 interleukins,which were named in the order of their discovery.Many of the interleukins listed form homodi-meric compounds and use the c and/or c chains in their receptors.(Cell 132,p.324)Cytokines II describes the remainder of the numerically named interleukins,many of which were discovered during the last decade.Due to the complexity of the heterodimeric ligands and receptors used by some of these factors,they present a unique challenge in the elucidation of their function during health and disease.(Cell 132,p.500)Cytokines III reviews the TNF family.Two important features of this group include the homotrimeric motif for both the ligands and the receptors and the capacity for bi-directional signaling.Targeting this family of inflammatory modulators has revolutionized the treatment of autoimmune disorders such as rheumatoid arthritis.(Cell 132,p.900)Cytokines IV includes many of the factors discovered prior to the current scheme for interleukin nomenclature.For historical reasons,the origi-nal names are still in use.Note that many of these factors share receptors with other interleukins,such as IL-7R and gp130,which are used by TSLP and IL-6,respectively.(Cell 132,p.1062)1062.e1 Cell 132,March 21,2008 2008 Elsevier Inc.DOI 10.1016/j.cell.2008.02.024SnapShot:Cytokines IVCristina M.Tato and Daniel J.CuaSchering-Plough Biopharma(Formerly DNAX Research),Palo Alto,CA 94304,USAAbbreviationsDTH,delayed type hypersensitivity;FLT-3,fms-like tyrosine kinase-3;GM-CSF,granulocyte-macrophage colony-stimulating factor;IFN,interferon;DC,dendritic cells;NK,natural killer cells;LIF,leukemia inhibitory factor;MIF,macrophage migration inhibitory factor;OSM,oncostatin M;TGF,transforming growth factor beta;Treg,regulatory T cells;TSLP,thymic stromal lymphopoietin.ReFeReNCeSBloom,B.R.,and Bennett,B.(1968).Migration inhibitory factor associated with delayed-type hypersensitivity.Fed.Proc.27,1315.Li,M.O.,Wan,Y.Y.,Sanjabi,S.,Robertson,A.K.,and Flavell,R.A.(2006).Transforming growth factor-beta regulation of immune responses.Annu.Rev.Immunol.24,99146.Liu,Y.J.,Soumelis,V.,Watanabe,N.,Ito,T.,Wang,Y.H.,Malefyt Rde,W.,Omori,M.,Zhou,B.,and Ziegler,S.F.(2007).TSLP:An epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation.Annu.Rev.Immunol.25,193219.Noppert,S.J.,Fitzgerald,K.A.,and Hertzog,P.J.(2007).The role of type I interferons in TLR responses.Immunol.Cell Biol.85,446457.OShea,J.J.,Tato,C.M.,and Siegel,R.(2008).Principles of immune recognition:Cytokines and cytokine receptors.In Clinical Immunology,3rd Edition,R.R.Rich,W.T.Shearer,T.A.Fleischer,H.W.Schroeder,C.M.Weyand,and A.J.Frew,eds.(Amsterdam:Elsevier).Rubtsov,Y.P.,and Rudensky,A.Y.(2007).TGFbeta signalling in control of T-cell-mediated self-reactivity.Nat.Rev.Immunol.7,443453.Severa,M.,and Fitzgerald,K.A.(2007).TLR-mediated activation of type I IFN during antiviral immune responses:Fighting the battle to win the war.Curr.Top.Microbiol.Immunol.316,167192.Shi,X.,Leng,L.,Wang,T.,Wang,W.,Du,X.,Li,J.,McDonald,C.,Chen,Z.,Murphy,J.W.,Lolis,E.,et al.(2006).CD44 is the signaling component of the macrophage migra-tion inhibitory factor-CD74 receptor complex.Immunity 25,595606.Young,H.A.,and Bream,J.H.(2007).IFN-gamma:Recent advances in understanding regulation of expression,biological functions,and clinical applications.Curr.Top.Microbiol.Immunol.316,97117.