Neutralization of Interleukin-16 Protects Nonobese Diabetic Mice From Autoimmune Type 1 Diabetes by a CCL4-Dependent Mechanism

Meagher, Craig; Beilke, Josh; Arreaza, Guillermo; Mi, Qing Sheng; Chen, Wei; Salojin, Konstantin V.; Horst, Noah; Cruikshank, William W.; Delovitch, Terry L.

doi:10.2337/db09-0131

Cited by 39 publications

(39 citation statements)

References 49 publications

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“…Its chemoattractive role for CD4þ T cells and DC is well known (28), and it has been shown to be involved in T-cell recruitment in the pancreas of NOD mice (29). These data as well as the preferential localization of CD4þ T cell and DC populations in the Ti-BALT are good arguments for a direct role of this cytokine in T-cell recruitment in these lymphoid structures.…”

Section: Discussionmentioning

confidence: 56%

Characterization of Chemokines and Adhesion Molecules Associated with T cell Presence in Tertiary Lymphoid Structures in Human Lung Cancer

et al. 2011

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De novo formation of tertiary lymphoid structures (TLS) has been described in lung cancers. Intratumoral TLS seem to be functional and are associated with a long-term survival for lung cancer patients, suggesting that they represent an activation site for tumor-specific T cells. Here, we characterized T-cell recruitment to TLS in human lung cancer to identify the adhesion molecules and chemoattractants orchestrating this migration. We found that most TLS T cells were CD62Lþ and mainly of CD4þ memory phenotype, but naive T cells were highly enriched in these structures as compared with the rest of the tumor. A specific gene expression signature associated with T cell presence was identified in TLS, which included chemokines (CCL19, CCL21, CXCL13, CCL17, CCL22, and IL16), adhesion molecules (ICAM-2, ICAM-3, VCAM-1, and MAdCAM-1) and integrins (alphaL, alpha4, and alphaD). The presence of the corresponding receptors on TLS T cells was confirmed. Intratumoral PNAdþ high endothelial venules also were exclusively associated with TLS and colocalized with CD62Lþ lymphocytes. Together, these data bring new insights into the T-cell recruitment to intratumoral TLS and suggest that blood T cell enter into TLS via high endothelial venules, which represent a new gateway for T cells to the tumor. Findings identify the molecules that mediate migration of tumor-specific T cells into TLS where T cell priming occurs, suggesting new strategies to enhance the efficacy of cancer immunotherapies.

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Section: Discussionmentioning

confidence: 56%

Characterization of Chemokines and Adhesion Molecules Associated with T cell Presence in Tertiary Lymphoid Structures in Human Lung Cancer

et al. 2011

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“…Previous studies have indicated that IL16 and IL18 are pro-inflammatory cytokines involved in the pathogenesis of diabetes [13,[18][19][20]. The significant role of low-grade inflammation has been confirmed in type 2 diabetes.…”

Section: Discussionmentioning

confidence: 73%

IL16 and IL18 gene polymorphisms in women with gestational diabetes

Tarnowski

Wieczorek²,

Dziedziejko

et al. 2017

Ginekol Pol

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Objectives: Gestational diabetes mellitus is a carbohydrate intolerance that occurs during pregnancy. Various inflammatory mediators are considered to be risk factors leading to GDM development. Among them are pro-inflammatory cytokines, such as IL16 and IL18. The aim of this study was to examine the association between IL16 and IL18 polymorphisms and GDM. Material and methods:This study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance (NGT). All samples were genotyped in duplicate using allelic discrimination assays with TaqMan® probes.Results: We observed that there was a decreased frequency of IL16 rs4778889 CC genotype carriers among women with GDM (CC vs. CT + TT: OR = 0.14; 95% CI = 0.02-1.15; p = 0.034). However, there was no significant difference in the distribution of alleles (C vs. T: OR = 0.81; 95% CI = 0.54-1.21; p = 0.30). There was a decreased frequency of the IL18 rs187238 G allele among GDM women (G vs. C: OR = 0.71; 95% CI = 0.53-0.96; p = 0.027). We also observed a decreased frequency of the IL18 rs1946518 T allele among women with GDM; however, this difference had only borderline statistical significance. We observed an association between IL18 rs187238, rs1946518 and BMI in pregnant women. Conclusions:The results of this study suggest that IL18 rs187238 and rs1946518 polymorphisms may be associated with an increased risk of GDM as well as with BMI in pregnant women.

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“…13 Furthermore, antibody-mediated neutralization of IL-16 leads to protection of NOD mice from type I diabetes. 14 Another cytokine with increased mRNA expression in T-cells from newly diagnosed compared with chronic ITP was TWEAK ( Figure 2F). The differential expression of this cytokine was also reflected at the protein level in plasma ( Figure 2G).…”

Section: Resultsmentioning

confidence: 99%

Differences in gene expression and cytokine levels between newly diagnosed and chronic pediatric ITP

Jernås

Hou

Célind

et al. 2013

Blood

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Neutralization of Interleukin-16 Protects Nonobese Diabetic Mice From Autoimmune Type 1 Diabetes by a CCL4-Dependent Mechanism

Cited by 39 publications

References 49 publications

Characterization of Chemokines and Adhesion Molecules Associated with T cell Presence in Tertiary Lymphoid Structures in Human Lung Cancer

Characterization of Chemokines and Adhesion Molecules Associated with T cell Presence in Tertiary Lymphoid Structures in Human Lung Cancer

IL16 and IL18 gene polymorphisms in women with gestational diabetes

Differences in gene expression and cytokine levels between newly diagnosed and chronic pediatric ITP

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