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Derp1-modified dendritic cells attenuate allergic inflammation by regulating the development of T helper type1(Th1)/Th2 cells and regulatory T cells in a murine model of allergic rhinitis.
Mol Immunol. 2017 10; 90:172-181.MI

Abstract

The CD4+CD25+Foxp3+ regulatory T cells (Tregs) are known to regulate Th2-induced allergic rhinitis (AR). In this study, we evaluated the efficacy of Derp1-modified dendritic cells (DCs) in AR immunotherapy. Derp1 was synthesized and transfected into DCs to generate Derp1-modified DCs. Phenotypes of Derp1-modified DCs were analyzed with flow cytometry using antibodies against DC markers CD11c, CD11b, CD59, CD103 and Toll-like receptor 1(TLR1). Four groups of subject mice were formed; the controls were treated with immature DCs, while the AR mice models were sensitized with Derp1(AR) and treated with DCs(DC-AR) or Derp1-modified DCs (Derp1DC-AR). The frequency of sneezing and scratching, eosinophil cell count, and Th1/Th2 ratio in the spleen were measured for all groups. The percentage of CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells was measured using flow cytometry; serum IgE, IgG1, and histamine were measured using enzyme-linked immunosorbent assay; expression levels of transcription factors T-bet, GATA3, Foxp3+ and IL-10 were analyzed using reverse transcription-polymerase chain reaction, and Western blot used in analyzed expression of Foxp3+ and IL-10 in nasal mucosa. Treatment with Derp1-modified DCs ameliorated the allergic response. The Derp1DC-AR group had significantly lower eosinophil cell count and the IgE, IgG1, and histamine levels than the AR and DC-AR groups, and higher mRNA levels of Th1 transcription factors T-bet, IL-10 and Foxp3 in nasal mucosa than DC-AR mice, but Th2 transcription factors GATA3 mRNA expression level has the opposite results. Furthermore, the Th1/Th2 ratio and percentage of CD4+CD25+Foxp3+ Tregs was significantly lower in the AR group (p<0.05), but higher in the Derp1DC-AR group than in the control group (p<0.01). Thus, the Derp1-modified DCs increased the percentage of CD4+CD25+Foxp3+Tregs and influenced the balance of Th1/Th2, showing an immunotherapeutic effect against AR.

Authors+Show Affiliations

Department of Otolaryngology, Tongji Hospital, Tongji University, Shanghai 200065, China. Electronic address: yu_shaoqing@163.com.Department of Otolaryngology, Tongji Hospital, Tongji University, Shanghai 200065, China.Department of Otolaryngology, Tongji Hospital, Tongji University, Shanghai 200065, China.Department of Otolaryngology, Huadong Hospital, Fudan University, Shanghai 200040, China.Department of Otolaryngology, Huadong Hospital, Fudan University, Shanghai 200040, China.Department of Otolaryngology, Huadong Hospital, Fudan University, Shanghai 200040, China.Department of Otolaryngology, Huadong Hospital, Fudan University, Shanghai 200040, China. Electronic address: nosezhang@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28802126

Citation

Yu, Shaoqing, et al. "Derp1-modified Dendritic Cells Attenuate Allergic Inflammation By Regulating the Development of T Helper type1(Th1)/Th2 Cells and Regulatory T Cells in a Murine Model of Allergic Rhinitis." Molecular Immunology, vol. 90, 2017, pp. 172-181.
Yu S, Han B, Liu S, et al. Derp1-modified dendritic cells attenuate allergic inflammation by regulating the development of T helper type1(Th1)/Th2 cells and regulatory T cells in a murine model of allergic rhinitis. Mol Immunol. 2017;90:172-181.
Yu, S., Han, B., Liu, S., Wang, H., Zhuang, W., Huang, Y., & Zhang, R. (2017). Derp1-modified dendritic cells attenuate allergic inflammation by regulating the development of T helper type1(Th1)/Th2 cells and regulatory T cells in a murine model of allergic rhinitis. Molecular Immunology, 90, 172-181. https://doi.org/10.1016/j.molimm.2017.07.015
Yu S, et al. Derp1-modified Dendritic Cells Attenuate Allergic Inflammation By Regulating the Development of T Helper type1(Th1)/Th2 Cells and Regulatory T Cells in a Murine Model of Allergic Rhinitis. Mol Immunol. 2017;90:172-181. PubMed PMID: 28802126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Derp1-modified dendritic cells attenuate allergic inflammation by regulating the development of T helper type1(Th1)/Th2 cells and regulatory T cells in a murine model of allergic rhinitis. AU - Yu,Shaoqing, AU - Han,Bing, AU - Liu,Shuangxi, AU - Wang,Hong, AU - Zhuang,Wenjie, AU - Huang,Yu, AU - Zhang,Ruxin, Y1 - 2017/08/09/ PY - 2017/02/07/received PY - 2017/07/19/revised PY - 2017/07/31/accepted PY - 2017/8/13/pubmed PY - 2017/11/8/medline PY - 2017/8/13/entrez KW - Allergic rhinitis KW - CD4(+)CD25(+)Foxp3(+) regulatory T cells KW - DC vaccine KW - Dendritic cells KW - Der p1 KW - Th1/Th2 SP - 172 EP - 181 JF - Molecular immunology JO - Mol. Immunol. VL - 90 N2 - The CD4+CD25+Foxp3+ regulatory T cells (Tregs) are known to regulate Th2-induced allergic rhinitis (AR). In this study, we evaluated the efficacy of Derp1-modified dendritic cells (DCs) in AR immunotherapy. Derp1 was synthesized and transfected into DCs to generate Derp1-modified DCs. Phenotypes of Derp1-modified DCs were analyzed with flow cytometry using antibodies against DC markers CD11c, CD11b, CD59, CD103 and Toll-like receptor 1(TLR1). Four groups of subject mice were formed; the controls were treated with immature DCs, while the AR mice models were sensitized with Derp1(AR) and treated with DCs(DC-AR) or Derp1-modified DCs (Derp1DC-AR). The frequency of sneezing and scratching, eosinophil cell count, and Th1/Th2 ratio in the spleen were measured for all groups. The percentage of CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells was measured using flow cytometry; serum IgE, IgG1, and histamine were measured using enzyme-linked immunosorbent assay; expression levels of transcription factors T-bet, GATA3, Foxp3+ and IL-10 were analyzed using reverse transcription-polymerase chain reaction, and Western blot used in analyzed expression of Foxp3+ and IL-10 in nasal mucosa. Treatment with Derp1-modified DCs ameliorated the allergic response. The Derp1DC-AR group had significantly lower eosinophil cell count and the IgE, IgG1, and histamine levels than the AR and DC-AR groups, and higher mRNA levels of Th1 transcription factors T-bet, IL-10 and Foxp3 in nasal mucosa than DC-AR mice, but Th2 transcription factors GATA3 mRNA expression level has the opposite results. Furthermore, the Th1/Th2 ratio and percentage of CD4+CD25+Foxp3+ Tregs was significantly lower in the AR group (p<0.05), but higher in the Derp1DC-AR group than in the control group (p<0.01). Thus, the Derp1-modified DCs increased the percentage of CD4+CD25+Foxp3+Tregs and influenced the balance of Th1/Th2, showing an immunotherapeutic effect against AR. SN - 1872-9142 UR - https://www.unboundmedicine.com/medline/citation/28802126/Derp1_modified_dendritic_cells_attenuate_allergic_inflammation_by_regulating_the_development_of_T_helper_type1_Th1_/Th2_cells_and_regulatory_T_cells_in_a_murine_model_of_allergic_rhinitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-5890(17)30445-5 DB - PRIME DP - Unbound Medicine ER -