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

Journal of Autoimmunity
Fernanda V DuraesS Hugues

Abstract

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.

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Citations

Aug 16, 2016·Nature Reviews. Neurology·Manoj K Mishra, V Wee Yong
Nov 29, 2016·Nature Reviews. Immunology·Tim WorbsReinhold Förster
Aug 5, 2017·Arthritis & Rheumatology·Ramzi NehmarPhilippe Georgel
Jul 19, 2019·European Journal of Immunology·Arnaud GarnierJean-Charles Guéry
Aug 11, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christopher SieThomas Korn
Jan 11, 2020·Immunology and Cell Biology·Jing-Yi LinLi-Fang Wang
Mar 31, 2017·Mediators of Inflammation·James CrooksFrancesca Fallarino
May 31, 2017·Clinical Reviews in Allergy & Immunology·Carlo Selmi
May 11, 2019·Scientific Reports·Vineet KumarBrian A Zabel
Jul 19, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Herena EixarchCarmen Espejo
Jul 28, 2019·Proceedings of the National Academy of Sciences of the United States of America·Lital SeverIdit Shachar
Nov 27, 2016·Seminars in Immunopathology·Christopher Sie, Thomas Korn
Aug 6, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Indumathi ManoharanSanthakumar Manicassamy

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Methods Mentioned

BETA
flow cytometry

Software Mentioned

Prism
FlowJo
GraphPad

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