ICOS gene haplotypes correlate with IL10 secretion and multiple sclerosis evolution

Castelli, Luca; Comi, Cristoforo; Chiocchetti, Annalisa; Nicola, Stefania; Mesturini, Riccardo; Giordano, Mara; D’Alfonso, Sandra; Cerutti, Elisa; Galimberti, Daniela; Fenoglio, Chiara; Tesser, Fabiana; Yagi, Junji; Rojo, José María; Perla, Franco; Leone, Maurizio; Scarpini, Elio; Monaco, Francesco; Dianzani, Umberto

doi:10.1016/j.jneuroim.2007.03.022

Cited by 23 publications

(24 citation statements)

References 38 publications

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“…Our study found linkage disequilibria between the polymorphisms ICOSc.602A>C, ICOSc.1624C>T, and ICOSc.2373G>C similar to those described by the Italian group [19] We cannot yet provide an explanation for this finding. As a matter of fact, the AA genotype of the ICOS gene is supposed to impair the expression of ICOS molecule [19] and thus impair the T cell-mediated response and T-cell dependent maturation of B-cells.…”

Section: Discussionsupporting

confidence: 50%

“…In the present study, we extended our investigation to subsequent ICOS gene polymorphisms which were recently described as functional ones [17,19] and were shown to be associated with susceptibility to multiple sclerosis [19] and outcome after renal [18] or hematopoietic stem cell transplantation [29], but not to melanoma [30]. [19], the frequency of the AA genotype was significantly lower in MS patients with relapsing-remitting disease than in controls, and those patients had a lower relapse rate and MS severity score.…”

Section: Discussionmentioning

confidence: 77%

“…[19], the frequency of the AA genotype was significantly lower in MS patients with relapsing-remitting disease than in controls, and those patients had a lower relapse rate and MS severity score.…”

Section: Discussionmentioning

confidence: 81%

“…The ICOSc.1624C>T polymorphism was shown to influence ICOS mRNA level [17] and the ICOSc.602A>C, ICOSc.1624C>T, and ICOSc.2373G>C SNPs influence functions of the ICOS gene [19]. The ICOS ISV1+173T>C polymorphism, located close to the CTLA-4 gene, has been reported to affect the expression of CTLA-4 isoforms [17].…”

Section: Introductionmentioning

confidence: 98%

“…Several polymorphisms have been found in the ICOS gene: two microsatellite in the fourth intron and 31 single-nucleotide polymorphisms (SNPs) (http:// //www.hapmap.org). None of the described ICOS SNPs leads to changes in amino acid, while a few have been demonstrated to be functional variants [17][18][19][20]. The chromosomal region of 2q33 harboring the CD28, CTLA-4, and ICOS gene family has been described as carrying predisposing genes for several autoimmune diseases [19,[21][22][23] and, recently, for cancer [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

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<i>ICOS</i> gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population

Karabon¹,

Jedynak²,

Tomkiewicz³

et al. 2011

Folia Histochem Cytobiol.

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Abstract:There is strong evidence that altered immunological function entails an increased risk of B-cell chronic lymphocytic leukemia (B-CLL). The main mechanism of an anti-tumor response depends on T-cell activation. Unlike the constitutively expressed CD28, inducible costimulatory molecule (ICOS) is expressed on the T-cell surface after activation. ICOS enhances all the basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, the upregulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B cells. ICOS is essential for both efficient interaction between T and B cells and normal antibody responses to T cell-dependent antigens. It does not upregulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Our previous results indicated the ICOS gene has a role as a susceptibility locus to B-CLL. Therefore an extended study was undertaken to evaluate the association between four ICOS polymorphisms (which were recently described as functional ones) and susceptibility to B-CLL in the Polish population. A case-control study of 296 individuals, including 146 B-CLL patients, was conducted on four polymorphisms in the ICOS gene. Genotyping of the polymorphisms ICOS ISV1+173T>C (rs10932029), ICOSc.1624C>T (rs10932037), ICOSc.2373G>C (rs4675379), and ICOSc.602A>C (rs10183087) was carried out using allelic discrimination methods with the TaqMan ® SNP Genotyping Assay. There were no statistically significant differences in the allele, genotype, or haplotype distributions between B-CLL patients and healthy controls for any of the investigated polymorphic markers in the ICOS gene.

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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<i>ICOS</i> gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population

Karabon¹,

Jedynak²,

Tomkiewicz³

et al. 2011

Folia Histochem Cytobiol.

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Reverse signaling using an inducible costimulator to enhance immunogenic function of dendritic cells

Tang

Qin

Zhang

et al. 2009

Cell. Mol. Life Sci.

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A costimulatory signal from an inducible costimulator (ICOS) of T cells plays a critical role in immunological homeostasis. This study shows that the interaction of ICOSIg and its ligand (ICOSL) on mouse bone marrow-derived dendritic cells (DCs) induces a p38-MAPK dependent elevation of interleukin 6 (IL-6). It also enhances phagocytosis and the antigen-presentation function of DCs in vitro, further favoring cell-mediated immunity in vivo. As seen for other types of costimulator molecules expressed in the T cells in the CD28 family, it is shown here for the first time that ICOS can also deliver reverse signals through its ligand to ICOSL-expressing cells. These reverse signals in turn transfer positive immunogenic information to bone marrow-derived DCs. Our work therefore provides new recognition of an ICOSL/ICOS signal pathway in immunity and also supplies more evidence that this ICOSL/ICOS signal pathway is a reasonable target for therapeutic drugs.

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Self-tolerance in multiple sclerosis

Gonsette

2012

Acta Neurol Belg

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During the last decade, several defects in self-tolerance have been identified in multiple sclerosis. Dysfunction in central tolerance leads to the thymic output of antigen-specific T cells with T cell receptor alterations favouring autoimmune reactions. In addition, premature thymic involution results in a reduced export of naïve regulatory T cells, the fully suppressive clone. Alterations in peripheral tolerance concern costimulatory molecules as well as transcriptional and epigenetic mechanisms. Recent data underline the key role of regulatory T cells that suppress Th1 and Th17 effector cell responses and whose immunosuppressive activity is impaired in patients with multiple sclerosis. Those recent observations suggest that a defect in self-tolerance homeostasis might be the primary mover of multiple sclerosis leading to subsequent immune attacks, inflammation and neurodegeneration. The concept of multiple sclerosis as a consequence of the failure of central and peripheral tolerance mechanisms to maintain a self-tolerance state, particularly of regulatory T cells, may have therapeutic implications. Restoring normal thymic output and suppressive functions of regulatory T cells appears an appealing approach. Regulatory T cells suppress the general local immune response via bystander effects rather than through individual antigen-specific responses. Interestingly, the beneficial effects of currently approved immunomodulators (interferons β and glatiramer acetate) are associated with a restored regulatory T cell homeostasis. However, the feedback regulation between Th1 and Th17 effector cells and regulatory T cells is not so simple and tolerogenic mechanisms also involve other regulatory cells such as B cells, dendritic cells and CD56bright natural killer cells.

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ICOS gene haplotypes correlate with IL10 secretion and multiple sclerosis evolution

Cited by 23 publications

References 38 publications

<i>ICOS</i> gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population

<i>ICOS</i> gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population

Reverse signaling using an inducible costimulator to enhance immunogenic function of dendritic cells

Self-tolerance in multiple sclerosis

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