Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors.Available evidence supports CD6,a lymphocyte surface receptor mostly expressed by T cells,as ...Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors.Available evidence supports CD6,a lymphocyte surface receptor mostly expressed by T cells,as a putative target in autoimmunity.Accordingly,a humanized anti-CD6 antibody has been assayed for the treatment of certain autoimmune disorders,including psoriasis.Here,we present novel evidence in mice and humans for a direct involvement of CD6 in psoriasis pathophysiology.First,an attenuated form of imiquimod-induced psoriasis-like skin inflammation was demonstrated in CD6-deficient mice,as deduced from lower epidermal thickness and local reduced production of pro-inflammatory cytokines,namely,interleukin-17A.Thus,isolated CD4+CD62L+T cells from CD6-deficient mice displayed decreased in vitro T-helper type 17 polarization.Second,a statistically significant association between CD6 single-nucleotide polymorphisms(rs17824933,rs11230563 and rs12360861)and more severe forms of psoriasis was demonstrated in a cohort of 304 patients at three public hospitals from the metropolitan area of Barcelona.Taken together,these results provide new supportive evidence of the contribution of the CD6 lymphocyte receptor in psoriasis at both experimental and clinical levels.展开更多
Type 1 diabetes(T1D),also referred to as insulin-dependent diabetes mellitus,is a debilitating disease that follows the destruction of pancreatic insulin-producingβcells by autologous T-cells.T1D primarily affects ch...Type 1 diabetes(T1D),also referred to as insulin-dependent diabetes mellitus,is a debilitating disease that follows the destruction of pancreatic insulin-producingβcells by autologous T-cells.T1D primarily affects children and has a strong genetic component,with>50 susceptibility loci identified,including HLA-DQβchains.1 However,the striking differences between European regions with similar genetic backgrounds and a sharp rise in T1D incidence in developed countries over the last several decades suggest that environmental factor(s)also play a relevant etiopathogenic role.2 Given the accumulating evidence linking the gut microbiota to protection against metabolic diseases,3 Mariño et al.4 recently tested the hypothesis that short-chain fatty acids(SCFAs),which are the end products of fermentation of dietary fibers by anaerobic intestinal microbiota,can protect genetically susceptible mice from developing T1D.Interestingly,the authors found that diets enriched in acetate or butyrate(two of the main SCFAs)can protect animals from developing diabetes through different and complementary cellular mechanisms.Such findings significantly enhance our understanding of the role of diet and gut microbiota in the development of autoimmune diseases and indicate that the use of medicinal foods may be a cost-effective treatment against T1D and other autoimmune diseases with a cellular component.Given that current anti-T1D approaches(which focus on prevention or modulation of the adaptive specific immune response against autoantigens)have been generally disappointing,5 such a new and refreshing strategy has attracted a great deal of attention(reviewed in Ref.2).展开更多
基金supported by grants from the Spanish Ministerio de Economía y Competitividad(Plan Nacional I+D+i,SAF2013-46151-R and SAF2016-80535-R to FL),co-financed by the European Development Regional Fund‘A way to achieve Europe’ERDFsupported by the Sara Borrell fellowship CD15/00016 from Instituto de Salud Carlos Ⅲ.
文摘Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors.Available evidence supports CD6,a lymphocyte surface receptor mostly expressed by T cells,as a putative target in autoimmunity.Accordingly,a humanized anti-CD6 antibody has been assayed for the treatment of certain autoimmune disorders,including psoriasis.Here,we present novel evidence in mice and humans for a direct involvement of CD6 in psoriasis pathophysiology.First,an attenuated form of imiquimod-induced psoriasis-like skin inflammation was demonstrated in CD6-deficient mice,as deduced from lower epidermal thickness and local reduced production of pro-inflammatory cytokines,namely,interleukin-17A.Thus,isolated CD4+CD62L+T cells from CD6-deficient mice displayed decreased in vitro T-helper type 17 polarization.Second,a statistically significant association between CD6 single-nucleotide polymorphisms(rs17824933,rs11230563 and rs12360861)and more severe forms of psoriasis was demonstrated in a cohort of 304 patients at three public hospitals from the metropolitan area of Barcelona.Taken together,these results provide new supportive evidence of the contribution of the CD6 lymphocyte receptor in psoriasis at both experimental and clinical levels.
基金The work by FL is supported by grants from the Worldwide Cancer Research(14-1275)FundacióLa MaratóTV3(201319-30)and Spanish Ministerio de Economía y Competitividad(Plan Nacional I+D+i,SAF2013-46151-R and SAF2016-80535-R)-co-financed by European Development Regional Fund‘A way to achieve Europe’ERDF.FA holds Sara Borrell(CD15/00016)and M-AES(MV16/00002)fellowships from Instituto de Salud Carlos III.TA is supported by the Cultural Mission of the Royal Embassy of Saudi Arabia(Qassim University).
文摘Type 1 diabetes(T1D),also referred to as insulin-dependent diabetes mellitus,is a debilitating disease that follows the destruction of pancreatic insulin-producingβcells by autologous T-cells.T1D primarily affects children and has a strong genetic component,with>50 susceptibility loci identified,including HLA-DQβchains.1 However,the striking differences between European regions with similar genetic backgrounds and a sharp rise in T1D incidence in developed countries over the last several decades suggest that environmental factor(s)also play a relevant etiopathogenic role.2 Given the accumulating evidence linking the gut microbiota to protection against metabolic diseases,3 Mariño et al.4 recently tested the hypothesis that short-chain fatty acids(SCFAs),which are the end products of fermentation of dietary fibers by anaerobic intestinal microbiota,can protect genetically susceptible mice from developing T1D.Interestingly,the authors found that diets enriched in acetate or butyrate(two of the main SCFAs)can protect animals from developing diabetes through different and complementary cellular mechanisms.Such findings significantly enhance our understanding of the role of diet and gut microbiota in the development of autoimmune diseases and indicate that the use of medicinal foods may be a cost-effective treatment against T1D and other autoimmune diseases with a cellular component.Given that current anti-T1D approaches(which focus on prevention or modulation of the adaptive specific immune response against autoantigens)have been generally disappointing,5 such a new and refreshing strategy has attracted a great deal of attention(reviewed in Ref.2).
