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

Abstract:

: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 (∼50 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-κB, 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-κB 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-κB towards BL/LL pole of disease.

journal_name

Immunobiology

journal_title

Immunobiology

authors

Kumar S,Naqvi RA,Bhat AA,Rani R,Ali R,Agnihotri A,Khanna N,Rao DN

doi

10.1016/j.imbio.2013.05.004

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

1488-96

issue

12

eissn

0171-2985

issn

1878-3279

pii

S0171-2985(13)00099-5

journal_volume

218

pub_type

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