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Lectin-targeted dendritic cell immunotherapies against experimental autoimmune encephalitis/multiple sclerosis (CAM5P.242)
Journal article   Peer reviewed

Lectin-targeted dendritic cell immunotherapies against experimental autoimmune encephalitis/multiple sclerosis (CAM5P.242)

Divya Sagar, Catherine Foss, Zafar Khan, Martin Pomper and Pooja Jain
The Journal of immunology (1950), v 192(1_Supplement), pp 180-180.13
01 May 2014
DOI: https://doi.org/10.4049/jimmunol.192.Supp.180.13

Abstract

Abstract The molecular mechanisms of how circulating dendritic cells (DCs) access the CNS across the blood-brain barrier (BBB) remains to be investigated. During neuroinflammation, DCs transmigrate across the BBB in the presence of chemoattractants, particularly CCL2, and initiate immune response. We showed through near-infrared imaging that DC accumulation into lesions within the CNS correlated with severity of inflammation during experimental autoimmune encephalitis (EAE). Actin polymerization on DCs upon CCL2 exposure indicated a migratory phenotype. Transmigration of DCs was paracellular and more efficient than T cells in vitro. To selectively attenuate DC transmigration, we sought to study expression of DC specific C type lectin receptors- CD205 & CD206 (Type I), CD207, -209, -303, CLEC4A, -9A, -10A & -12A (Type II). Different DC subsets- myeloid (mDC), plasmacytoid (pDC) and monocyte-derived (MDDC) had a unique enrichment of lectin receptors and each subset utilized a different receptor to adhere and transmigrate in the presence of CCL2. Phosphoproteomics revealed that these receptors when triggered, activate molecular events known to be involved in actin dynamics, thus substantiating their role in DC transmigration. Importantly, in EAE mice these lectins were validated targets for inhibiting DC transmigration. Thus, the prospect of selectively regulating DC entry into the CNS will open up new treatments against disease pathogenesis and propagation in multiple sclerosis.

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