Interleukin-1(IL-1),referred to as two distinct proteins,IL-1αand IL-1β,was first described almost 50 years ago.1 IL-1αand IL-1βrepresent immediate early innate cytokines critically involved in alarming and activa...Interleukin-1(IL-1),referred to as two distinct proteins,IL-1αand IL-1β,was first described almost 50 years ago.1 IL-1αand IL-1βrepresent immediate early innate cytokines critically involved in alarming and activating the host defense system.2 Therefore,any impairment of IL-1 signaling pathways often leads to devastating outcomes,such as autoimmunity and autoinflammation,dysmetabolism,cardiovascular disorders,and cancer.2 Many advances in targeting IL-1 in immune therapies have been achieved;for example,the IL-1-blocking agents anakinra(IL-1 receptor antagonist,IL-1Ra),canakinumab(anti-IL-1βmAb),and MABp1(anti-IL-1αmAb)have been approved for clinical use or are being evaluated.2 Remarkably,the CANTOS study,which included over 10,000 patients,showed that blocking IL-1βnot only reduced atherosclerosis-related cardiovascular mortality but was also effective in inflammatory diseases related to lung cancer,arthrosis,and gout.3.展开更多
Zika virus(ZIKV)and Japanese encephalitis virus(JEV)are closely related flaviviruses,ZIKV circulates in the population that has been JEV vaccinated in Southeast Asian countries.This alerts that a pre-existing immunity...Zika virus(ZIKV)and Japanese encephalitis virus(JEV)are closely related flaviviruses,ZIKV circulates in the population that has been JEV vaccinated in Southeast Asian countries.This alerts that a pre-existing immunity to JEV would impact ZIKV infection and/or pathogenesis.Herein we showed that the preexisting immunity to JEV SA14-14-2 vaccination provided an ample protection against non-lethal or lethal dose of ZIKV infection in mice.This was in sharp contrast to the passive immunization of JEV antibodies,which failed to affect ZIKV infection or pathogenesis in mice,albeit these antibodies exhibited cross-reactivity and antibody dependent enhancement(ADE)of ZIKV infection in vitro.Furthermore,we determined that JEV vaccine-elicited CD8+T cells were required to mediate the heterotypic protection of ZIKV infection,which cross-reacted to ZIKV E and NS5 antigens(E294-302and NS52839-2848).Adoptive transfer of these CD8+T cells could partially protect the mice from ZIKV challenge.Therefore,although short of epidemiological evidence,these results suggested that cross-reactive CD8+T cells activated by JEV vaccination could protect potential ZIKV infection in human populations.展开更多
文摘Interleukin-1(IL-1),referred to as two distinct proteins,IL-1αand IL-1β,was first described almost 50 years ago.1 IL-1αand IL-1βrepresent immediate early innate cytokines critically involved in alarming and activating the host defense system.2 Therefore,any impairment of IL-1 signaling pathways often leads to devastating outcomes,such as autoimmunity and autoinflammation,dysmetabolism,cardiovascular disorders,and cancer.2 Many advances in targeting IL-1 in immune therapies have been achieved;for example,the IL-1-blocking agents anakinra(IL-1 receptor antagonist,IL-1Ra),canakinumab(anti-IL-1βmAb),and MABp1(anti-IL-1αmAb)have been approved for clinical use or are being evaluated.2 Remarkably,the CANTOS study,which included over 10,000 patients,showed that blocking IL-1βnot only reduced atherosclerosis-related cardiovascular mortality but was also effective in inflammatory diseases related to lung cancer,arthrosis,and gout.3.
基金supported by Grants from CAS,China(XDB29030301)Natural Sciences Foundation of Shanghai,China(19ZR1463100)National Science and Technology Major Project,China(2018ZX10101004002004)to H.T.
文摘Zika virus(ZIKV)and Japanese encephalitis virus(JEV)are closely related flaviviruses,ZIKV circulates in the population that has been JEV vaccinated in Southeast Asian countries.This alerts that a pre-existing immunity to JEV would impact ZIKV infection and/or pathogenesis.Herein we showed that the preexisting immunity to JEV SA14-14-2 vaccination provided an ample protection against non-lethal or lethal dose of ZIKV infection in mice.This was in sharp contrast to the passive immunization of JEV antibodies,which failed to affect ZIKV infection or pathogenesis in mice,albeit these antibodies exhibited cross-reactivity and antibody dependent enhancement(ADE)of ZIKV infection in vitro.Furthermore,we determined that JEV vaccine-elicited CD8+T cells were required to mediate the heterotypic protection of ZIKV infection,which cross-reacted to ZIKV E and NS5 antigens(E294-302and NS52839-2848).Adoptive transfer of these CD8+T cells could partially protect the mice from ZIKV challenge.Therefore,although short of epidemiological evidence,these results suggested that cross-reactive CD8+T cells activated by JEV vaccination could protect potential ZIKV infection in human populations.
