title: Elevated levels of serum IL-12 and IL-18 are associated with lower frequencies of CD4(+)CD25 (high)FOXP3 (+) regulatory t cells in young patients with type 1 diabetes.
abstract: Type 1 diabetes is thought to involve chronic inflammation, which is manifested by the activation and expression of different inflammatory mediators. IL-12 and IL-18 are two cytokines that have been shown to exert strong proinflammatory activity and have been implicated in the pathogenesis of type 1 diabetes in mice and humans. The overproduction of proinflammatory mediators is controlled by specialized T cell subset, namely regulatory T cells that express FOXP3 transcription factor. Since IL-12 and IL-18 mediate inflammatory response and Tregs exhibit anti-inflammatory potential, we aimed to examine their reciprocal relationship in patients with type 1 diabetes. The study group consisted of 47 children diagnosed with type 1 diabetes and 28 healthy individuals. Serum levels of IL-12 and IL-18 were measured by ELISA, and the peripheral blood CD4(+)CD25(high) FOXP3(+) regulatory T cell frequencies were analyzed by flow cytometry. Patients with type 1 diabetes had a decreased percentage of circulating CD4(+)CD25(high)FOXP3(+) Tregs in comparison to their healthy counterparts. In addition, they produced more IL-12 and IL-18 than children from the control group. Concentrations of these cytokines positively correlated with one another, as well as with CRP and HbA1c. Moreover, the negative association between IL-12, IL-18, CRP serum levels, and the frequency of regulatory CD4(+)CD25(high)FOXP3(+) Tregs was observed. IL-12 and IL-18 may have direct or indirect impact on regulatory T cell subset, which may contribute to their reduced frequency in peripheral blood of patients with type 1 diabetes mellitus.
authors.affiliation: Department of Immunology, Medical University of Gdańsk, Dębinki 1, 80-210, Gdańsk, Poland, akinomab@gumed.edu.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Ryba-Stanisławowska
authors.forename: Karolina
authors.initials: K
authors.lastname: Rybarczyk-Kapturska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Myśliwiec
authors.forename: Jolanta
authors.initials: J
authors.lastname: Myśliwska
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count / Q000379:methods; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000175:diagnosis; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D018664:Interleukin-12 / Q000097:blood*; D020382:Interleukin-18 / Q000097:blood*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C000589760:IL18 protein, human; C508017:IL2RA protein, human; D020382:Interleukin-18; D053645:Interleukin-2 Receptor alpha Subunit; D018664:Interleukin-12