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Abstract:

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.

Registro:

Documento: Artículo
Título:Parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway
Autor:Correale, J.; Farez, M.F.
Filiación:Department of Neurology, Dr. Raul Carrea Institute for Neurological Research, Foundation for the Fight Against Infant Neurological Illnesses, Montaneses 2325, 1428 Buenos Aires, Argentina
Palabras clave: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
Año:2013
Volumen:191
Número:7
Página de inicio:3827
Página de fin:3837
DOI: http://dx.doi.org/10.4049/jimmunol.1301110
Título revista:Journal of Immunology
Título revista abreviado:J. Immunol.
ISSN:00221767
CODEN:JOIMA
CAS:albendazole, 54965-21-8; alcohol dehydrogenase, 9031-72-5; gamma interferon, 82115-62-6; interleukin 12, 138415-13-1; ivermectin, 70288-86-7; mitogen activated protein kinase, 142243-02-5; retinoic acid, 302-79-4; retinol dehydrogenase, 9033-53-8; toll like receptor 2, 203811-81-8; ALDH1A2 protein, human, 1.2.1.36; Alcohol Dehydrogenase, 1.1.1.1; Antigens, Helminth; Cytokines; FOXP3 protein, human; Forkhead Transcription Factors; Inflammation Mediators; Receptors, Retinoic Acid; Retinal Dehydrogenase, 1.2.1.36; SOCS3 protein, human; Suppressor of Cytokine Signaling Proteins; Tretinoin, 5688UTC01R
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v191_n7_p3827_Correale

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Citas:

---------- APA ----------
Correale, J. & Farez, M.F. (2013) . Parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway. Journal of Immunology, 191(7), 3827-3837.
http://dx.doi.org/10.4049/jimmunol.1301110
---------- CHICAGO ----------
Correale, J., Farez, M.F. "Parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway" . Journal of Immunology 191, no. 7 (2013) : 3827-3837.
http://dx.doi.org/10.4049/jimmunol.1301110
---------- MLA ----------
Correale, J., Farez, M.F. "Parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway" . Journal of Immunology, vol. 191, no. 7, 2013, pp. 3827-3837.
http://dx.doi.org/10.4049/jimmunol.1301110
---------- VANCOUVER ----------
Correale, J., Farez, M.F. Parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway. J. Immunol. 2013;191(7):3827-3837.
http://dx.doi.org/10.4049/jimmunol.1301110