The effect of Dermatophagoides pteronyssinus group 7 allergen (Der p 7) on dendritic cells and its role in T cell polarization

详细信息    查看全文

• 作者：Jaw-Ji Tsai^a ; ^b ; ^c ; Hsin-Chieh Wang^b ; Chih-Liang Chiu^d ; En-Chih Liao^e ; ^{enchih@mmc.edu.tw" class="auth_mail" title="E-mail the corresponding author} ; ^{postdream8@hotmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：DCs ; dendritic cells ; Th2 ; T helper type 2 ; Der p 7 ; Dermatophagoides pteronyssinus group 7 ; DC-SIGN ; dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin ; BMDCs ; bone marrow-derived dendritic cells ; MDDCs ; monocyte-derived dendritic cells ; TLR4 ; Toll-like receptor 4 ; LPS ; lipopolysaccharide ; MD-2 ; myeloid differentiation-2 ; CLRs ; C-type lectin-like receptors ; PVDF ; polyvinylidene difluoride ; ELISA ; Enzyme-linked immunosorbent assay ; GM-CSF ; Granulocyte-macrophage colo
• 刊名：Immunobiology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：221
• 期：11
• 页码：1319-1328
• 全文大小：1956 K

文摘

The innate signaling pathway for Th2 immunity activated by inhaled allergens has not been well defined. Dendritic cells (DCs) can use their innate pattern-recognition Toll-like receptors and C-type lectin receptors to generate innate immunity and influence adaptive responses. The aim of this study was to investigate the glycoform of Dermatophagoides pteronyssinus group 7 allergen (Der p 7) and its functional interaction with dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). Both bone marrow-derived dendritic cells (BMDCs) derived from mice and monocyte-derived DCs (MDDCs) derived from human peripheral blood mononuclear cells (PBMCs) were used to investigate the function of Der p 7. Dendritic cells derived from THP1 were used to investigate the glycol form of Der p 7. Der p 7 interacted with DC-SIGN as recognized by immunoprecipitation and glycoprotein staining, and its function was partially inhibited by deglycosylation. When BMDCs were cultured with Der p 7, the secretion of IL-6 and gene expressions of IL-6, OX40 L and Jagged-1 were increased. IL4⁺/CD4⁺ T cells could be induced by Der p 7, however IFN-γ⁺/CD4⁺ T cells were down-regulated. The effects of Der p 7 on DCs were down-regulated in the presence of DC-SIGN or TLR4 antibodies and deglycosylation. rDer p 7 enhanced the DC differentiation of CD80 and CD86. The effects of Der p 7 pulsed-MDDCs on IL4⁺/CD4⁺ and IFN-γ⁺/CD4⁺ T-cell differentiation of human PBMCs were significantly increased after Der p 7 stimulation and decreased by DC-SIGN antibody inhibition. In conclusion, the Der p 7 is a glycoprotein and its function was partially through glycan binding. BMDCs could be activated by Der p 7 through TLR4 and DC-SIGN, and followed by the expression of OX40 ligand (OX40L) and Jagged-1, the expressions of IL4⁺/CD4⁺ cells were enhanced. These findings identify a previously unrecognized function of Der p 7 and establish a link between innate TLR4/C-type lectin receptors and adaptive Th2 immunity.