PMID- 33891644
OWN - NLM
STAT- MEDLINE
DCOM- 20210930
LR  - 20210930
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 16
IP  - 4
DP  - 2021
TI  - Priming of myelin-specific T cells in the absence of dendritic cells results in 
      accelerated development of Experimental Autoimmune Encephalomyelitis.
PG  - e0250340
LID - 10.1371/journal.pone.0250340 [doi]
LID - e0250340
AB  - Experimental autoimmune encephalomyelitis (EAE) is an established animal model of 
      multiple sclerosis (MS). Inflammatory CD4+ T cell responses directed against CNS 
      antigens, including myelin proteolipid protein (PLP), are key mediators of EAE. 
      Dendritic cells (DCs) are critical for the induction of T cell responses against 
      infectious agents. However, the importance of DCs in priming self-reactive CD4+ T 
      cells in autoimmune disease such as MS has been unclear. To determine the 
      requirement of DCs in PLP-specific CD4+ T cell responses and EAE, we genetically 
      deleted CD11c+ DCs in PLP T cell receptor (TCR) transgenic SJL mice 
      constitutively. DC deficiency did not impair the development, selection or the 
      pathogenic function of PLP-specific CD4+ T cells in these mice, and resulted in 
      accelerated spontaneous EAE compared to DC sufficient controls. In addition, 
      using a genetic approach to ablate DCs conditionally in SJL mice, we show that 
      CD11c+ DCs were dispensable for presenting exogenous or endogenous myelin antigen 
      to PLP-specific T cells and for promoting pro-inflammatory T cell responses and 
      severe EAE. Our findings demonstrate that constitutive or conditional ablation of 
      CD11c+ DCs diminished self-tolerance to PLP autoantigen. They further show that 
      in the absence of DCs, non-DCs can efficiently present CNS myelin antigens such 
      as PLP to self-reactive T cells, resulting in accelerated onset of spontaneous or 
      induced EAE.
FAU - Luu, Thaiphi
AU  - Luu T
AD  - Department of Microbiology & Immunology, Penn State College of Medicine, Hershey, 
      Pennsylvania, United States of America.
FAU - Cheung, Julie F
AU  - Cheung JF
AUID- ORCID: 0000-0003-1346-0930
AD  - Department of Microbiology & Immunology, Penn State College of Medicine, Hershey, 
      Pennsylvania, United States of America.
FAU - Baccon, Jennifer
AU  - Baccon J
AD  - Department of Pathology, Penn State College of Medicine, Hershey, Pennsylvania, 
      United States of America.
AD  - Department of Neurosurgery, Penn State College of Medicine, Hershey, 
      Pennsylvania, United States of America.
FAU - Waldner, Hanspeter
AU  - Waldner H
AUID- ORCID: 0000-0001-7844-1162
AD  - Department of Microbiology & Immunology, Penn State College of Medicine, Hershey, 
      Pennsylvania, United States of America.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210423
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Autoantigens)
SB  - IM
MH  - Animals
MH  - Autoantigens/immunology
MH  - CD4-Positive T-Lymphocytes/cytology/*immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/cytology/*immunology
MH  - Encephalomyelitis, Autoimmune, Experimental/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Myelin Sheath/*immunology
PMC - PMC8064509
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/04/24 06:00
MHDA- 2021/10/01 06:00
PMCR- 2021/04/23
CRDT- 2021/04/23 17:18
PHST- 2020/12/30 00:00 [received]
PHST- 2021/04/05 00:00 [accepted]
PHST- 2021/04/23 17:18 [entrez]
PHST- 2021/04/24 06:00 [pubmed]
PHST- 2021/10/01 06:00 [medline]
PHST- 2021/04/23 00:00 [pmc-release]
AID - PONE-D-20-41003 [pii]
AID - 10.1371/journal.pone.0250340 [doi]
PST - epublish
SO  - PLoS One. 2021 Apr 23;16(4):e0250340. doi: 10.1371/journal.pone.0250340. 
      eCollection 2021.