pDC therapy induces recovery from EAE by recruiting endogenous pDC to sites of CNS inflammation

TY - JOUR

T1 - pDC therapy induces recovery from EAE by recruiting endogenous pDC to sites of CNS inflammation

AU - Duraes, Fernanda V

AU - Lippens, Carla

AU - Steinbach, Karin

AU - Dubrot, Juan

AU - Brighouse, Dale

AU - Bendriss-Vermare, Nathalie

AU - Issazadeh-Navikas, Shohreh

AU - Merkler, Doron

AU - Hugues, Stephanie

N1 - Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Plasmacytoid dendritic cells (pDCs) exhibit both innate and adaptive functions. In particular they are the main source of type I IFNs and directly impact T cell responses through antigen presentation. We have previously demonstrated that during experimental autoimmune encephalomyelitis (EAE) initiation, myelin-antigen presentation by pDCs is associated with suppressive Treg development and results in attenuated EAE. Here, we show that pDCs transferred during acute disease phase confer recovery from EAE. Clinical improvement is associated with migration of injected pDCs into inflamed CNS and is dependent on the subsequent and selective chemerin-mediated recruitment of endogenous pDCs to the CNS. The protective effect requires pDC pre-loading with myelin antigen, and is associated with the modulation of CNS-infiltrating pDC phenotype and inhibition of CNS encephalitogenic T cells. This study may pave the way for novel pDC-based cell therapies in autoimmune diseases, aiming at specifically modulating pathogenic cells that induce and sustain autoimmune inflammation.

AB - Plasmacytoid dendritic cells (pDCs) exhibit both innate and adaptive functions. In particular they are the main source of type I IFNs and directly impact T cell responses through antigen presentation. We have previously demonstrated that during experimental autoimmune encephalomyelitis (EAE) initiation, myelin-antigen presentation by pDCs is associated with suppressive Treg development and results in attenuated EAE. Here, we show that pDCs transferred during acute disease phase confer recovery from EAE. Clinical improvement is associated with migration of injected pDCs into inflamed CNS and is dependent on the subsequent and selective chemerin-mediated recruitment of endogenous pDCs to the CNS. The protective effect requires pDC pre-loading with myelin antigen, and is associated with the modulation of CNS-infiltrating pDC phenotype and inhibition of CNS encephalitogenic T cells. This study may pave the way for novel pDC-based cell therapies in autoimmune diseases, aiming at specifically modulating pathogenic cells that induce and sustain autoimmune inflammation.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.jaut.2015.08.014

DO - 10.1016/j.jaut.2015.08.014

M3 - Journal article

C2 - 26341385

SN - 0896-8411

VL - 67

SP - 8

EP - 18

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

ER -