Chemokines as Drivers of the Autoimmune Destruction in Type 1 Diabetes: Opportunity for Therapeutic Intervention in Consideration of an Optimal Treatment Schedule

Christen, Urs; Kimmel, Ruta

doi:10.3389/fendo.2020.591083

Cited by 29 publications

(26 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The latter aspect is consistent with other reports (Muller et al, 2021;Tang et al, 2021;Wu et al, 2021) and provides a rationale to focus our subsequent analyses on the earlier 48-h time point. Here, a broad assessment of inflammation-associated TCS proteins (92 analytes) revealed a notably restrained inflammatory response involving the chemokines CXCL10 and CXCL11 (previously implicated in T1D pathogenesis; Christen and Kimmel, 2020;Homann, 2015) but only marginal levels of IFNg (a potent inducer of CXCL10/11) and minor downregulation of multiple proteins associated positively and negatively with b cell survival and diabetes development (Bhandage et al, 2018;Hanson et al, 2014;Kondegowda et al, 2015;Liadis et al, 2007;Mellado-Gil et al, 2011;Vendrell and Chacon, 2013;Figures 1E and 1F).…”

Section: Resultsmentioning

confidence: 91%

Limited extent and consequences of pancreatic SARS-CoV-2 infection

et al. 2022

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 91%

Limited extent and consequences of pancreatic SARS-CoV-2 infection

et al. 2022

View full text Add to dashboard Cite

“…In addition, findings of a previous study suggested that blocking of CXCL10 can impede the expansion of peripheral Ag-specific T cells and hinder their migration to the islet microenvironment ( 90 ). Furthermore, the CXCL10 blockade aborts Ag-specific injury of β cells in the islet microenvironment and abrogates T1DM ( 91 ). In this regard, it was shown that, after the treatment of CXCL10 DNA vaccination (pCAGGS-CXCL10), the spontaneous diabetic mice could induce the production of anti-CXCL10 Ab and inhibit the occurrence of spontaneous diabetes in vivo ( 92 , 93 ).…”

Section: Discussionmentioning

confidence: 99%

Chemokines in Type 1 Diabetes Mellitus

et al. 2022

View full text Add to dashboard Cite

BackgroundPrevious studies suggested that chemokines may play an important role in the formation and mediation of immune microenvironments of patients affected by Type 1 Diabetes Mellitus (T1DM). The aim of this study was to summarise available evidence on the associations of different chemokines with T1DM.MethodsFollowing PRISMA guidelines, we systematically searched in PubMed, Web of Science, Embase and Cochrane Library databases for studies on the associations of different chemokines with T1DM. The effect size of the associations were the standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) of the chemokines concentrations, calculated as group differences between the T1DM patients and the controls. These were summarized using network meta-analysis, which was also used to rank the chemokines by surface under cumulative ranking curve (SUCRA) probabilities.ResultsA total of 32 original studies on the association of different chemokines with T1DM were identified. Fifteen different chemokine nodes were compared between 15,683 T1DM patients and 15,128 controls, and 6 different chemokine receptor nodes were compared between 463 T1DM patients and 460 controls. Circulating samples (blood, serum, and plasma) showed that concentrations of CCL5 and CXCL1 were significantly higher in the T1DM patients than in the controls (SMD of 3.13 and 1.50, respectively). On the other hand, no significant difference in chemokine receptors between T1DM and controls was observed. SUCRA probabilities showed that circulating CCL5 had the highest rank in T1DM among all the chemokines investigated.ConclusionThe results suggest that circulating CCL5 and CXCL1 may be promising novel biomarkers of T1DM. Future research should attempt to replicate these findings in longitudinal studies and explore potential mechanisms underlying this association.

show abstract

“…This drives their migration to sites of inflammation [ 73 ], such as CXCL9 and CXCL10 producing islets [ 61 ]. While studies on the expression of CXCL10 in serum of pre-diabetic at risk individuals or patients with T1D showed divergent results, the vast majority of studies both in humans and mouse models showed enhanced CXCL10 levels related to T1D (summarized in [ 34 . In line with these results, the beta cell-specific expression of CXCL10 caused islet infiltration in T1D-resistant mice [ 153 ], while its blockade delayed the disease in NOD mice [ 134 ] and the combination therapy with anti-CD3 antibody lead to persistent remission in different mouse models of T1D [ 101 ].…”

Section: Chemokinesmentioning

confidence: 99%