LymphedemaV1, Main, Exploration, bibRecord, 007E46

Transcriptional Control of Impaired Th1 Responses in Patent Lymphatic Filariasis by T-Box Expressed in T Cells and Suppressor of Cytokine Signaling Genes

Identifieur interne : 007E46 ( Main/Exploration ); précédent : 007E45; suivant : 007E47

Transcriptional Control of Impaired Th1 Responses in Patent Lymphatic Filariasis by T-Box Expressed in T Cells and Suppressor of Cytokine Signaling Genes

Auteurs : Subash Babu ; V. Kumaraswami ; Thomas B. Nutman

Source :

Infection and Immunity [ 0019-9567 ] ; 2005.

RBID : PMC:1111868

Descripteurs français

English descriptors

KwdEn :
- Adult, Antigens, Helminth (immunology), DNA-Binding Proteins (genetics), DNA-Binding Proteins (physiology), Elephantiasis, Filarial (immunology), Female, Forkhead Transcription Factors, GATA3 Transcription Factor, Humans, Interferon-gamma (biosynthesis), Interleukin-10 (biosynthesis), Intracellular Signaling Peptides and Proteins (genetics), Male, Middle Aged, Nuclear Proteins (genetics), Proteins (genetics), Repressor Proteins (genetics), Suppressor of Cytokine Signaling 1 Protein, Suppressor of Cytokine Signaling 3 Protein, Suppressor of Cytokine Signaling Proteins, T-Box Domain Proteins, Th1 Cells (immunology), Trans-Activators (genetics), Trans-Activators (physiology), Transcription Factors (genetics), Transcription Factors (physiology), Transcription, Genetic.
MESH :
- chemical , biosynthesis : Interferon-gamma, Interleukin-10.
- chemical , genetics : DNA-Binding Proteins, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Proteins, Repressor Proteins, Trans-Activators, Transcription Factors.
- chemical , immunology : Antigens, Helminth.
- chemical , physiology : DNA-Binding Proteins, Trans-Activators, Transcription Factors.
- immunology : Elephantiasis, Filarial, Th1 Cells.
- Adult, Female, Forkhead Transcription Factors, GATA3 Transcription Factor, Humans, Male, Middle Aged, Suppressor of Cytokine Signaling 1 Protein, Suppressor of Cytokine Signaling 3 Protein, Suppressor of Cytokine Signaling Proteins, T-Box Domain Proteins, Transcription, Genetic.

Abstract

T-bet (T-box expressed in T cells) and GATA-3 are transcription factors that play a critical role in the development of Th1 and Th2 cells, as do genes of the SOCS (suppressor of cytokine signaling) family, albeit indirectly. Another transcription factor, Foxp3, is a master regulator of natural regulatory T cells (Tregs). To identify the role of these factors in impaired Th1 responses of patent filarial infection, analysis of cytokine, SOCS, and transcription factor mRNA expression was performed on purified T cells of filaria-infected individuals (n = 6) and uninfected controls (n = 6). As expected (and in contrast to cells of uninfected individuals), there was a significant depression of gamma interferon (IFN-γ) and a concomitant increase in interleukin-4 (IL-4), IL-5, and IL-10 mRNA expression following stimulation with parasite antigen (BmA) but not with a polyclonal T-cell (anti-CD3) stimulus. T-bet (but not GATA-3) was expressed at significantly lower levels in cells of filaria-infected individuals in response to BmA compared with those from the uninfected group, accounting, at least partially, for the diminished IFN-γ expression. Second, we found no significant differences in expression of Foxp3 between the two groups, although induction of Foxp3 expression correlated with induced expression levels of IL-10, implicating Tregs in the IL-10 expression seen. Finally, parasite-specific T-cell expression of SOCS-1, SOCS-5, and SOCS-7 was significantly diminished among infected patients; in contrast, expression of SOCS-3 increased. Our data therefore indicate that the impaired Th1 responses observed in patent lymphatic filariasis are associated with decreased expression of T-bet, SOCS-1, SOCS-5, and SOCS-7 and increased expression of SOCS-3 in T cells.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1111868

DOI: 10.1128/IAI.73.6.3394-3401.2005
PubMed: 15908366
PubMed Central: 1111868

Affiliations:

Le document en format XML

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<term>Antigens, Helminth (immunology)</term>
<term>DNA-Binding Proteins (genetics)</term>
<term>DNA-Binding Proteins (physiology)</term>
<term>Elephantiasis, Filarial (immunology)</term>
<term>Female</term>
<term>Forkhead Transcription Factors</term>
<term>GATA3 Transcription Factor</term>
<term>Humans</term>
<term>Interferon-gamma (biosynthesis)</term>
<term>Interleukin-10 (biosynthesis)</term>
<term>Intracellular Signaling Peptides and Proteins (genetics)</term>
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<term>Middle Aged</term>
<term>Nuclear Proteins (genetics)</term>
<term>Proteins (genetics)</term>
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<term>Suppressor of Cytokine Signaling 3 Protein</term>
<term>Suppressor of Cytokine Signaling Proteins</term>
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<term>Th1 Cells (immunology)</term>
<term>Trans-Activators (genetics)</term>
<term>Trans-Activators (physiology)</term>
<term>Transcription Factors (genetics)</term>
<term>Transcription Factors (physiology)</term>
<term>Transcription, Genetic</term>
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<term>Adulte d'âge moyen</term>
<term>Antigènes d'helminthe (immunologie)</term>
<term>Facteur de transcription GATA-3</term>
<term>Facteurs de transcription (génétique)</term>
<term>Facteurs de transcription (physiologie)</term>
<term>Facteurs de transcription Forkhead</term>
<term>Femelle</term>
<term>Filariose lymphatique (immunologie)</term>
<term>Humains</term>
<term>Interféron gamma (biosynthèse)</term>
<term>Interleukine-10 (biosynthèse)</term>
<term>Lymphocytes auxiliaires Th1 (immunologie)</term>
<term>Mâle</term>
<term>Protéine-1 suppressive de la signalisation des cytokines</term>
<term>Protéine-3 suppressive de la signalisation des cytokine</term>
<term>Protéines (génétique)</term>
<term>Protéines SOCS</term>
<term>Protéines de liaison à l'ADN (génétique)</term>
<term>Protéines de liaison à l'ADN (physiologie)</term>
<term>Protéines de répression (génétique)</term>
<term>Protéines et peptides de signalisation intracellulaire (génétique)</term>
<term>Protéines nucléaires (génétique)</term>
<term>Protéines à domaine boîte-T</term>
<term>Transactivateurs (génétique)</term>
<term>Transactivateurs (physiologie)</term>
<term>Transcription génétique</term>
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<term>Interleukin-10</term>
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<term>Intracellular Signaling Peptides and Proteins</term>
<term>Nuclear Proteins</term>
<term>Proteins</term>
<term>Repressor Proteins</term>
<term>Trans-Activators</term>
<term>Transcription Factors</term>
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<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>DNA-Binding Proteins</term>
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<term>Protéines</term>
<term>Protéines de liaison à l'ADN</term>
<term>Protéines de répression</term>
<term>Protéines et peptides de signalisation intracellulaire</term>
<term>Protéines nucléaires</term>
<term>Transactivateurs</term>
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<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes d'helminthe</term>
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<term>Female</term>
<term>Forkhead Transcription Factors</term>
<term>GATA3 Transcription Factor</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
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<term>Adulte d'âge moyen</term>
<term>Facteur de transcription GATA-3</term>
<term>Facteurs de transcription Forkhead</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mâle</term>
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<front><div type="abstract" xml:lang="en"><p>T-bet (T-box expressed in T cells) and GATA-3 are transcription factors that play a critical role in the development of Th1 and Th2 cells, as do genes of the SOCS (suppressor of cytokine signaling) family, albeit indirectly. Another transcription factor, Foxp3, is a master regulator of natural regulatory T cells (Tregs). To identify the role of these factors in impaired Th1 responses of patent filarial infection, analysis of cytokine, SOCS, and transcription factor mRNA expression was performed on purified T cells of filaria-infected individuals (<italic>n</italic>
 = 6) and uninfected controls (<italic>n</italic>
 = 6). As expected (and in contrast to cells of uninfected individuals), there was a significant depression of gamma interferon (IFN-γ) and a concomitant increase in interleukin-4 (IL-4), IL-5, and IL-10 mRNA expression following stimulation with parasite antigen (BmA) but not with a polyclonal T-cell (anti-CD3) stimulus. T-bet (but not GATA-3) was expressed at significantly lower levels in cells of filaria-infected individuals in response to BmA compared with those from the uninfected group, accounting, at least partially, for the diminished IFN-γ expression. Second, we found no significant differences in expression of Foxp3 between the two groups, although induction of Foxp3 expression correlated with induced expression levels of IL-10, implicating Tregs in the IL-10 expression seen. Finally, parasite-specific T-cell expression of SOCS-1, SOCS-5, and SOCS-7 was significantly diminished among infected patients; in contrast, expression of SOCS-3 increased. Our data therefore indicate that the impaired Th1 responses observed in patent lymphatic filariasis are associated with decreased expression of T-bet, SOCS-1, SOCS-5, and SOCS-7 and increased expression of SOCS-3 in T cells.</p>
</div>
</front>
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<name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B." last="Nutman">Thomas B. Nutman</name>
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Transcriptional Control of Impaired Th1 Responses in Patent Lymphatic Filariasis by T-Box Expressed in T Cells and Suppressor of Cytokine Signaling Genes

Transcriptional Control of Impaired Th1 Responses in Patent Lymphatic Filariasis by T-Box Expressed in T Cells and Suppressor of Cytokine Signaling Genes

Source :

Descripteurs français

English descriptors

Abstract

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