IL-10 production from dendritic cells is associated with DC SIGN in human leprosy

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• 作者：Sudhir Kumar ; Raza Ali Naqvi ; Ajaz A. Bhat ; Richa Rani ; Riyasat Ali ; Abhishek Agnihotri ; Neena Khanna ; D.N. Rao
• 关键词：DC SIGN ; Leprosy ; ManLAM ; Mycobacterium leprae ; NF-魏B ; p300
• 刊名：Immunobiology
• 出版年：December, 2013
• 年：2013
• 卷：218
• 期：12
• 页码：1488-1496
• 全文大小：1640 K

文摘

The defective antigen presenting ability of antigen presenting cells (APCs) modulates host cytokines and co-stimulatory signals that may lead to severity of leprosy. In the present study, we sought to evaluate the phenotypic features of APCs along with whether DC SIGN (DC-specific intercellular adhesion molecule-grabbing nonintegrin) influences IL-10 production while moving from tuberculoid (BT/TT) to lepromatous (BL/LL) pole in leprosy pathogenesis. The study revealed an increased expression of DC SIGN on CD11c⁺ cells from BL/LL patients and an impaired form of CD83 (鈭?0 kDa). However, the cells after treatment with GM-CSF+IL-4+ManLAM showed an increased expression of similar form of CD83 on DCs. Upon treatment with ManLAM, DCs were found to show increased nuclear presence of NF-魏B, thus leading to higher IL-10 production. High IL-10 production from ManLAM treated PBMCs further suggested the role of DC SIGN in subverting the DCs function towards BL/LL pole of leprosy. Anti-DC SIGN treatment resulting in restricted nuclear ingression of NF-魏B as well as its acetylation along with enhanced T cell proliferation validated our findings. In conclusion, Mycobacterium leprae component triggers DC SIGN on DCs to induce production of IL-10 by modulating intracellular signalling pathway at the level of transcription factor NF-魏B towards BL/LL pole of disease.