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1、ReviewMiniFocus:RheuMatologyForreprintorders,pleasecontactreprints@future-science.comPleiotropictargets:theproblemofsharedsignalingcircuitryinrheumatoidarthritisdiseaseprogressionandprotectionTheimmuneresponseisrepletewithfeedbackcontrolatmanylevels.Theseprotect
2、ivecircuitsareevenfunctionalwithinthearthriticjoint,temperingdiseasetovaryingextents.Anoptimaltherapywouldinhibitautoimmuneprocesseswhilemaintainingprotectivecircuitry.However,manyofthecellsandproteinsthatserveasimportantmediatorsofdiseaseprogressionalsoplayanac
3、tiveroleintheseprotectivecircuits.Thehypothesisconsideredinthisreviewisthattheinadvertentinhibitionofprotectivecircuitryadverselyaffectsefficacy.Conversely,iftherapeuticscanbedesigned,whichavoidinhibitingknownregulatorycircuits,efficacywillbeimproved.Understandi
4、ngwheretheseprocessessharesignalingmoleculeswillbecrucialtothedevelopmentofthenextgenerationoftherapeutics.Thisreviewdiscussesthreewell-definedsignaltransductioncascades;IL-2,IFNgandTNF-a,anddemonstratewithintwocelltypes,Tcellsandmacrophages,howthesecytokinesmay
5、contributebothtoprotectionandtodiseaseprogression.Rheumatoidarthritis(RA)isachronicautoim-pathogenicmoleculeinhumanRA.ManyRobertIScheinmanmuneandinflammatorydiseaseofthejoints,otherclinicaltrials,whiledemonstratingdif-DepartmentofPharmaceuticalcharacterizedbysyn
6、oviocyteproliferationandferingefficaciesfortheblockadeofIL-1orIL-6,Sciences,UniversityofColoradotheinfiltrationofimmunecells.MacrophagesclearlydemonstratethatthesecytokinesalsoDenverAnschutzMedicalCampus,12850EastMontviewBoulevard,anddendriticcellspresentantigen
7、stoTcells.playanimportantroleindiseaseprogressionAurora,CO80045,USATcellsinteractwithBcellstopromotethepro-[3,4].ThesedataalsodemonstratethatnooneTel.:+13037243384E-mail:robert.scheinman@ductionofautoantibodies.Inaddition,theycytokineappearstopredominateinallins
8、tancesucdenver.eduinteractwithsynovialfibroblasts,macrophages,ofthedisease,asthereexistnonrespondersfordendriticcellsandneutrophilstopromotetheeachofthesetherapeutics