Parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway
We recently demonstrated better outcomes in helminth-infected multiple sclerosis (MS) patients, compared with uninfected ones. The present study evaluates the role of TLR2 and retinoic acid (RA) in parasite-driven protection in MS patients. RA serum levels were significantly higher in helminth-infec...
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2013
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v191_n7_p3827_Correale http://hdl.handle.net/20.500.12110/paper_00221767_v191_n7_p3827_Correale |
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paper:paper_00221767_v191_n7_p3827_Correale2023-06-08T14:46:57Z Parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway albendazole alcohol dehydrogenase cytokine gamma interferon interleukin 10 interleukin 12 interleukin 17 interleukin 23 interleukin 6 ivermectin mitogen activated protein kinase parasite antigen protein Adh1 protein RALDH2 protein SEA retinoic acid retinoic acid receptor retinol dehydrogenase suppressor of cytokine signaling 3 toll like receptor 2 transcription factor FOXP3 tumor necrosis factor alpha unclassified drug adult article autoimmunity cell activation clinical article cohort analysis controlled study cytokine production dendritic cell female gene expression gene silencing helminthiasis human human cell immunomodulation male multiple sclerosis nonhuman parasitosis priority journal prospective study protein blood level protein metabolism protein synthesis regulatory T lymphocyte Schistosoma mansoni signal transduction single drug dose Alcohol Dehydrogenase Antigens, Helminth Cytokines Dendritic Cells Female Forkhead Transcription Factors Humans Inflammation Mediators Male Models, Biological Multiple Sclerosis Parasitic Diseases Receptors, Retinoic Acid Retinal Dehydrogenase Signal Transduction Suppressor of Cytokine Signaling Proteins T-Lymphocytes, Regulatory Tretinoin We recently demonstrated better outcomes in helminth-infected multiple sclerosis (MS) patients, compared with uninfected ones. The present study evaluates the role of TLR2 and retinoic acid (RA) in parasite-driven protection in MS patients. RA serum levels were significantly higher in helminth-infected MS patients than in uninfected MS subjects or healthy controls. Genes involved in RA biosynthesis and metabolism, such as Adh1 and Raldh2, as well as RA receptors and IL-10, were induced in dendritic cells (DCs) via TLR2-dependent ERK signaling. This programmed DCs to induce FOXP3+ T regulatory cells and suppressed production of proinflammatory cytokines (IL-6, IL-12, IL-23, and TNF-α) via induction of suppressor of cytokine signaling 3(SOCS3), an effect mediated by soluble egg Ag (SEA) obtained from Schistosoma mansoni, and by RA. SEA-activated DCs also inhibited IL-17 and IFN-γ production through autoreactive T cells. These inhibitory effects were abrogated when SOCS3 gene expression was silenced, indicating that SEA-mediated signaling inhibited production of these cytokines by T cells, through a SOCS3-dependent pathway. Overall, helminth-related immunomodulation observed in MS patients was mediated by TLR2- and RA-dependent pathways, through two different mechanisms, as follows:1) induction of IL-10 and FOXP3+ T regulatory cells, and 2) suppression of proinflammatory cytokine production mediated by SOCS3. Copyright © 2013 by The American Association of Immunologists, Inc. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v191_n7_p3827_Correale http://hdl.handle.net/20.500.12110/paper_00221767_v191_n7_p3827_Correale |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
albendazole alcohol dehydrogenase cytokine gamma interferon interleukin 10 interleukin 12 interleukin 17 interleukin 23 interleukin 6 ivermectin mitogen activated protein kinase parasite antigen protein Adh1 protein RALDH2 protein SEA retinoic acid retinoic acid receptor retinol dehydrogenase suppressor of cytokine signaling 3 toll like receptor 2 transcription factor FOXP3 tumor necrosis factor alpha unclassified drug adult article autoimmunity cell activation clinical article cohort analysis controlled study cytokine production dendritic cell female gene expression gene silencing helminthiasis human human cell immunomodulation male multiple sclerosis nonhuman parasitosis priority journal prospective study protein blood level protein metabolism protein synthesis regulatory T lymphocyte Schistosoma mansoni signal transduction single drug dose Alcohol Dehydrogenase Antigens, Helminth Cytokines Dendritic Cells Female Forkhead Transcription Factors Humans Inflammation Mediators Male Models, Biological Multiple Sclerosis Parasitic Diseases Receptors, Retinoic Acid Retinal Dehydrogenase Signal Transduction Suppressor of Cytokine Signaling Proteins T-Lymphocytes, Regulatory Tretinoin |
| spellingShingle |
albendazole alcohol dehydrogenase cytokine gamma interferon interleukin 10 interleukin 12 interleukin 17 interleukin 23 interleukin 6 ivermectin mitogen activated protein kinase parasite antigen protein Adh1 protein RALDH2 protein SEA retinoic acid retinoic acid receptor retinol dehydrogenase suppressor of cytokine signaling 3 toll like receptor 2 transcription factor FOXP3 tumor necrosis factor alpha unclassified drug adult article autoimmunity cell activation clinical article cohort analysis controlled study cytokine production dendritic cell female gene expression gene silencing helminthiasis human human cell immunomodulation male multiple sclerosis nonhuman parasitosis priority journal prospective study protein blood level protein metabolism protein synthesis regulatory T lymphocyte Schistosoma mansoni signal transduction single drug dose Alcohol Dehydrogenase Antigens, Helminth Cytokines Dendritic Cells Female Forkhead Transcription Factors Humans Inflammation Mediators Male Models, Biological Multiple Sclerosis Parasitic Diseases Receptors, Retinoic Acid Retinal Dehydrogenase Signal Transduction Suppressor of Cytokine Signaling Proteins T-Lymphocytes, Regulatory Tretinoin Parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway |
| topic_facet |
albendazole alcohol dehydrogenase cytokine gamma interferon interleukin 10 interleukin 12 interleukin 17 interleukin 23 interleukin 6 ivermectin mitogen activated protein kinase parasite antigen protein Adh1 protein RALDH2 protein SEA retinoic acid retinoic acid receptor retinol dehydrogenase suppressor of cytokine signaling 3 toll like receptor 2 transcription factor FOXP3 tumor necrosis factor alpha unclassified drug adult article autoimmunity cell activation clinical article cohort analysis controlled study cytokine production dendritic cell female gene expression gene silencing helminthiasis human human cell immunomodulation male multiple sclerosis nonhuman parasitosis priority journal prospective study protein blood level protein metabolism protein synthesis regulatory T lymphocyte Schistosoma mansoni signal transduction single drug dose Alcohol Dehydrogenase Antigens, Helminth Cytokines Dendritic Cells Female Forkhead Transcription Factors Humans Inflammation Mediators Male Models, Biological Multiple Sclerosis Parasitic Diseases Receptors, Retinoic Acid Retinal Dehydrogenase Signal Transduction Suppressor of Cytokine Signaling Proteins T-Lymphocytes, Regulatory Tretinoin |
| description |
We recently demonstrated better outcomes in helminth-infected multiple sclerosis (MS) patients, compared with uninfected ones. The present study evaluates the role of TLR2 and retinoic acid (RA) in parasite-driven protection in MS patients. RA serum levels were significantly higher in helminth-infected MS patients than in uninfected MS subjects or healthy controls. Genes involved in RA biosynthesis and metabolism, such as Adh1 and Raldh2, as well as RA receptors and IL-10, were induced in dendritic cells (DCs) via TLR2-dependent ERK signaling. This programmed DCs to induce FOXP3+ T regulatory cells and suppressed production of proinflammatory cytokines (IL-6, IL-12, IL-23, and TNF-α) via induction of suppressor of cytokine signaling 3(SOCS3), an effect mediated by soluble egg Ag (SEA) obtained from Schistosoma mansoni, and by RA. SEA-activated DCs also inhibited IL-17 and IFN-γ production through autoreactive T cells. These inhibitory effects were abrogated when SOCS3 gene expression was silenced, indicating that SEA-mediated signaling inhibited production of these cytokines by T cells, through a SOCS3-dependent pathway. Overall, helminth-related immunomodulation observed in MS patients was mediated by TLR2- and RA-dependent pathways, through two different mechanisms, as follows:1) induction of IL-10 and FOXP3+ T regulatory cells, and 2) suppression of proinflammatory cytokine production mediated by SOCS3. Copyright © 2013 by The American Association of Immunologists, Inc. |
| title |
Parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway |
| title_short |
Parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway |
| title_full |
Parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway |
| title_fullStr |
Parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway |
| title_full_unstemmed |
Parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway |
| title_sort |
parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway |
| publishDate |
2013 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v191_n7_p3827_Correale http://hdl.handle.net/20.500.12110/paper_00221767_v191_n7_p3827_Correale |
| _version_ |
1768546145514029056 |