Cytokines III.PDF

See online version for abbreviations and references.900 Cell 132,March 7,2008 2008 Elsevier Inc.DOI 10.1016/j.cell.2008.02.023SnapShot:Cytokines IIICristina M.Tato and Daniel J.CuaSchering-Plough Biopharma(Formerly DNAX Research),Palo Alto,CA 94304,USACytokineReceptor SourceTargetsMajor FunctionDisease AssociationTNFMurine:TNFR,p55;TNFR,p75 Human:TNFR,p60;TNFR,p80Macrophages,monocytes,T cells,othersNeutrophils,macrophages,monocytes,endothelial cellsInflammatory;promotes activation and production of acute-phase proteins =disregulated fever;increased susceptibility to bacterial infection;enhanced resistance to LPS-induced septic shock =exacerbation of arthritis and colitisLTMurine:TNFR,p55;TNFR,p75 Human:TNFR,p60;TNFR,p80T cells,B cellsMany cell typesPromotes activation and cytotoxicity;development of lymph nodes and Peyers patches=defective response to bacterial pathogens;absence of peripheral lymph nodes and Peyers patchesLTLTRT cells,B cellsMyeloid cells,other cell types Peripheral lymph node development;proinflammatory=increased susceptibility to bacterial infection;absence of lymph nodes and Peyers patches =ectopic lymph node formationLIGHTaLTR,DcR3,HVEMActivated T cells,monocytes,DCsB cells,NK cells,DCs,other tissueCostimulatory;promotes CTL activity=defective CD8 T cell costimulationTWEAKFn14Monocytes,macrophages,endothelialTissue progenitors,epithelial,endothelialProinflammatory;promotes cell growth for tissue repair and remodelingAPRILTACI,BAFF-R,BCMAMacrophages,DCsB cell subsetsPromotes T cell-independent responses;B cell homeostasis and differentiation=impaired class switching to IgABAFF(BlyS)TACI,BAFF-R,BCMAMacrophages,DCs,astrocytesB cellsB cell maturation and survival=B cell lymphopenia;defective humoral immunity =SLE-like syndromeTL1ADcR3,DR3Macrophages,endothelial cellsActivated T cellsPromotes proliferation and cytokine productionGITRLaGITRDCs,macrophages,B cells,othersT regulatory cells,activated T cellsCostimulatoryOX40LaOX40Activated T cells,B cells,DCs,monocytesT cells,B cells,DCsCostimulatory;activation and migration of monocytes=impaired humoral responsesCD40La(CD154)CD40T cells,monocytes,macrophages,othersB cells,APCsCostimulatory;promotes T cell-dependent responses;B cell differentiation and class switching=defective antibody responses and germinal center formation;hyper-IgM syndrome =SLE-like syndromeFASLaFAS,DcR3Activated T cells,B cells,and NK cellsAPCs,many other cell typesRegulatory;pro apoptotic=lymphoproliferative disease and systemic autoimmunityCD27La(CD70)CD27Activated T cells,B cells,DCs,monocytesT cells,activated B cellsCostimulatoryCD30La(CD153)CD30Neutrophils,B cells,macrophages,activated T cellsT cells,B cellsCostimulatory;promotes proliferation and cytokine productionViral CD30 blocks Th1 response4-1BBLa41BBActivated T cells,B cells,DCs,mono-cytes,macrophagesActivated T cells,B cells,DCsCostimulatory;promotes activation and migration of monocytesTRAILaTRAIL-R1(DR4),R2(DR5),R3(DcR1),and R4(DcR2)Activated NK cells,T cellsMany cell typesCostimulatory;promotes NK cell functions;proapoptotic=defective NK-mediated antitumor response =enhanced responsiveness to autoantigensRANK Liganda (TRANCE)RANK receptor or osteoprotegrinT cells and osteoblastsOsteoclasts,many cell typesCostimulatory;promotes osteoclasto-genesis and cytokine production=osteopetrosis =osteoporosis aKnown to exhibit bidirectional signaling via the ligand as well as the receptor.900.e1 Cell 132,March 7,2008 2008 Elsevier Inc.DOI 10.1016/j.cell.2008.02.023SnapShot:Cytokines IIICristina M.Tato and Daniel J.CuaSchering-Plough Biopharma(Formerly DNAX Research),Palo Alto,CA 94304,USAAbbreviationsTNF,tumor necrosis factor alpha;DCs,dendritic cells;LT,lymphotoxin;APC,antigen-presenting cell;LIGHT,homologous to lymphotoxin,exhibits inducible expression,and competes with herpes simplex virus glycoprotein D for HVEM,a receptor expressed on T cells;HVEM,herpesvirus entry mediator;DcR,decoy receptor;TWEAK,TNF-related weak inducer of apoptosis;APRIL,a proliferation-inducing ligand;BAFF,B cell-activating factor;BCMA,B cell maturation protein A;TACI,transmembrane activator and CAML interactor;SLE,systemic lupus erythematosus;DR,death receptor;GITRL,glucocorticoid-induced TNF receptor ligand;TRAIL,TNF-like apoptosis-inducing ligand;RANK,receptor activator of NF-B.REFERENCESAbe,K.,Kurakin,A.,Mohseni-Maybodi,M.,Kay,B.,and Khosravi-Far,R.(2000).The complexity of TNF-related apoptosis-inducing ligand.Ann.N Y Acad.Sci.926,5263.Feldman,M.,Taylor,P.,Paleolog,E.,Brennan,F.M.,and Maini,R.N.(1998).Anti-TNF alpha therapy is useful in rheumatoid arthritis and Crohns disease:Analysis of the mechanism of action predicts utility in other diseases.Transplant.Proc.30,41264127.Le Pottier,L.,Sapir,T.,Bendaoud,B.,Youinou,P.,Shoenfeld,Y.,and Pers,J.O.(2007).Intravenous immunoglobulin and cytokines:Focus on tumor necrosis factor family members BAFF and APRIL.Ann.NY Acad.Sci.1110,426432.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).Paul,N.L.,and Ruddle,N.H.(1988).Lymphotoxin.Annu.Rev.Immunol.6,407438.Sun,M.,and Fink,P.J.(2007).A new class of reverse signaling costimulators belongs to the TNF family.J.Immunol.179,43074312.Tumanov,A.V.,Christiansen,P.A.,and Fu,Y.X.(2007).The role of lymphotoxin receptor signaling in diseases.Curr.Mol.Med.7,567578.Watts,T.H.(2005).TNF/TNFR family members in costimulation of T cell responses.Annu.Rev.Immunol.23,2368.