The role of IL-17 in many inflammatory and autoimmune diseases is now well established,with three currently registered anti-IL-17-targeted therapies.This story has taken place over a period of 20 years and led to the ...The role of IL-17 in many inflammatory and autoimmune diseases is now well established,with three currently registered anti-IL-17-targeted therapies.This story has taken place over a period of 20 years and led to the demonstration that a T cell product could regulate,and often amplify,the inflammatory response.The first results described the contribution of IL-17 to local features in arthritis.Then,understanding was extended to its systemic effects,with a focus on cardiovascular aspects.This review provides a historical perspective of these discoveries focused on arthritis,which started in 1995,followed 10 years later by the description of Th17 cells.Today,IL-17 inhibitors for three chronic inflammatory diseases have been registered.More options are now being tested in ongoing and future clinical trials.Inhibitors of IL-17 family members and Th17 cells ranging from antibodies to small molecules are under active development.The identification of patients with IL-17-driven disease is a key target for the improved selection of patients expected to have a strongly positive response.展开更多
Tumor necrosis factor(TNF)inhibitors have improved a lot the treatment of numerous diseases,with the well-known example of rheumatoid arthritis(RA).In the early 2000s,postmarketing data quickly revealed an alarming nu...Tumor necrosis factor(TNF)inhibitors have improved a lot the treatment of numerous diseases,with the well-known example of rheumatoid arthritis(RA).In the early 2000s,postmarketing data quickly revealed an alarming number of severe tuberculosis(TB)under such treatment.These findings were consistent with previous results in mice where TNF is essential for lymph node formation and granuloma organization.The effects of TNF inhibition on RA synovium structure are very similar to those on granuloma,with changes in cellular interactions,cytokine,and chemokine production.In addition to the role of TNF in granuloma,the interleukin(IL)-12/interferon(IFN)-γpathway is required for an efficient host defense against TB.Primary and secondary immunodeficiencies affecting this pathway lead to severe bacillus Calmette-Guérin(BCG)reaction or full TB.Any chronic inflammation as in RA induces a systemic Th1 defect that predisposes to TB through specific downregulation of the IL-12Rß2 chain.When TNF inhibitors are initiated,this transiently increases this risk of TB,through effects on cellular interactions in a latent TB granuloma.At a later stage,when a better control disease activity is obtained,the risk of TB is reduced but not abrogated.Given the clear benefit from TNF inhibition,latent TB infection screening at baseline is essential for an optimal safety.展开更多
文摘The role of IL-17 in many inflammatory and autoimmune diseases is now well established,with three currently registered anti-IL-17-targeted therapies.This story has taken place over a period of 20 years and led to the demonstration that a T cell product could regulate,and often amplify,the inflammatory response.The first results described the contribution of IL-17 to local features in arthritis.Then,understanding was extended to its systemic effects,with a focus on cardiovascular aspects.This review provides a historical perspective of these discoveries focused on arthritis,which started in 1995,followed 10 years later by the description of Th17 cells.Today,IL-17 inhibitors for three chronic inflammatory diseases have been registered.More options are now being tested in ongoing and future clinical trials.Inhibitors of IL-17 family members and Th17 cells ranging from antibodies to small molecules are under active development.The identification of patients with IL-17-driven disease is a key target for the improved selection of patients expected to have a strongly positive response.
基金supported in part by the IHU OPERA.This review is based on a talk given during the 17th International Congress of Immunology that took place on 19-23 October 2019 in Beijing,China。
文摘Tumor necrosis factor(TNF)inhibitors have improved a lot the treatment of numerous diseases,with the well-known example of rheumatoid arthritis(RA).In the early 2000s,postmarketing data quickly revealed an alarming number of severe tuberculosis(TB)under such treatment.These findings were consistent with previous results in mice where TNF is essential for lymph node formation and granuloma organization.The effects of TNF inhibition on RA synovium structure are very similar to those on granuloma,with changes in cellular interactions,cytokine,and chemokine production.In addition to the role of TNF in granuloma,the interleukin(IL)-12/interferon(IFN)-γpathway is required for an efficient host defense against TB.Primary and secondary immunodeficiencies affecting this pathway lead to severe bacillus Calmette-Guérin(BCG)reaction or full TB.Any chronic inflammation as in RA induces a systemic Th1 defect that predisposes to TB through specific downregulation of the IL-12Rß2 chain.When TNF inhibitors are initiated,this transiently increases this risk of TB,through effects on cellular interactions in a latent TB granuloma.At a later stage,when a better control disease activity is obtained,the risk of TB is reduced but not abrogated.Given the clear benefit from TNF inhibition,latent TB infection screening at baseline is essential for an optimal safety.
