کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6117083 | 1217160 | 2015 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
New TLR7 agonists with improved humoral and cellular immune responses
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
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چکیده انگلیسی
Toll-like receptor 7 (TLR7) agonists are of interest as vaccine adjuvants and cancer therapeutics. Therefore, development of new TLR7 agonists that can efficiently promote host immune responses without evoking side effects is of great importance. Here, we describe two new compounds, J4 and F4, which elicit intracellular signaling exclusively via TLR7. Interestingly, both J4 and F4 induced less cytokine secretion (IL-1β, IL-6, IL-10, IL-12p40, TNFα, and IL-12p70) from myeloid dendritic cells (mDCs) and monocytes than CL075 and R848; however, they all generated similar levels of phenotype maturation of antigen presenting cells (APCs), including plasmacytoid DCs. We further found that J4- and F4-induced APC activation was largely dependent on the activation of NF-κB and p38. Lastly, J4 and F4 could efficiently promote B cell proliferation and plasmablast differentiation as well as antigen-specific CD8+ T cell responses in human in vitro. Therefore, these new TLR7 agonists could be employed to facilitate the development of new therapeutics and vaccine adjuvants against cancers and microbial infections.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Immunology Letters - Volume 168, Issue 1, November 2015, Pages 89-97
Journal: Immunology Letters - Volume 168, Issue 1, November 2015, Pages 89-97
نویسندگان
Katherine C. Upchurch, José R. BoquÃn, Wenjie Yin, Yaming Xue, HyeMee Joo, Robert R. Kane, SangKon Oh,