کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6087322 1207356 2014 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of TNF receptor signaling by anti-TNFα biologicals primes naïve CD4+ T cells towards IL-10+ T cells with a regulatory phenotype and function
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Inhibition of TNF receptor signaling by anti-TNFα biologicals primes naïve CD4+ T cells towards IL-10+ T cells with a regulatory phenotype and function
چکیده انگلیسی


- Neutralization of TNFα during naïve CD4T cell activation enhances IL-10+ T cells.
- Anti-TNFα enhances IL-10+ T cells by inhibiting the interaction of TNFα with TNFRI.
- TNFα neutralization induces an extended regulatory gene profile.
- Naïve T cells primed in presence of anti-TNFα have enhanced suppressive capacity.

TNFα is a potent pro-inflammatory cytokine playing a pivotal role in several autoimmune diseases. Little is known about the mechanism of TNFα blocking agents on naïve T cell differentiation. Here, we report that neutralizing TNFα during priming of naïve CD4+ T cells by dendritic cells favors development of IL-10+ T helper cells. TNFα counteracts IL-10+ T cell priming mainly via TNFRI receptor signaling. While initial T cell activation was not affected, neutralization of TNFα negatively affected sustained T cell differentiation in later stages of T cell priming. Whole genome gene expression analysis revealed an extended regulatory gene profile for anti-TNFα-treated T cells. Indeed, neutralizing TNFα during naïve T cell priming enhanced the suppressive function of anti-TNFα-treated T cells. Taken together, inhibition of TNFα-TNFR interaction shifts the balance of Th cell differentiation towards IL-10 expressing suppressive T cells, which may be one of the beneficial mechanisms in TNFα blocking therapies.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinical Immunology - Volume 151, Issue 2, April 2014, Pages 136-145
نویسندگان
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