PMID- 29494692
OWN - NLM
STAT- MEDLINE
DCOM- 20180702
LR  - 20211204
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 3
DP  - 2018
TI  - IL-12/23p40 overproduction by dendritic cells leads to an increased Th1 and Th17 
      polarization in a model of Yersinia enterocolitica-induced reactive arthritis in 
      TNFRp55-/- mice.
PG  - e0193573
LID - 10.1371/journal.pone.0193573 [doi]
LID - e0193573
AB  - Dendritic cells (DCs) play critical functions in the initiation of immune 
      responses. Understanding their role in reactive arthritis (ReA) will help 
      delineate the pathogenesis of this arthropathy. In early studies, we detected 
      IL-12/23p40 deregulation in Yersinia entercolitica (Ye)-induced ReA in 
      TNFRp55-deficient (TNFRp55-/-) mice. In this study, we assessed the contribution 
      of DCs in this overproduction. First, greater levels of IL-12/23p40, IFN-gammaand 
      IL-17A were confirmed in supernatants of lipopolysaccharide (LPS)-stimulated 
      TNFRp55-/-splenocytes obtained on arthritis onset (day 14 after Ye infection). 
      Later, DCs were identified as a precise source of IL-12/23p40 since increased 
      frequency of splenic IL-12/23p40+DCs was detected in TNFRp55-/- mice. After 
      robust in vivo amplification of DCs by injection of Fms-like tyrosine kinase 
      3-Ligand (Flt3L)-transfected BL16 melanoma, DCs were purified. These cells 
      recapitulated the higher production of IL-12/23p40 under TNFRp55deficiency. In 
      agreement with these results, TNFRp55-/- DCs promoted Th1 and Th17 programs by 
      co-culture with WT CD4+lymphocytes. A mechanistic study demonstrated that JNK and 
      p38 MAPK pathways are involved in IL-12/23p40 overproduction in purified 
      TNFRp55-/- DCs as well as in the JAWS II cell line. This deregulation was once 
      again attributed to TNFRp55 deficiency since CAY10500, a specific inhibitor of 
      this pathway, compromised TNF-mediated IL-12/23p40 control in LPS-stimulated WT 
      DCs. Simultaneously, this inhibition reduced IL-10 production, suggesting its 
      role mediating IL-12/23p40 regulation by TNFRp55 pathway. These results provide 
      experimental data on the existence of a TNFRp55-mediated anti-inflammatory 
      circuit in DCs. Moreover, these cells may be considered as a novel target in the 
      treatment of ReA.
FAU - Mayordomo, Andrea Constanza
AU  - Mayordomo AC
AD  - Division de Inmunologia, Facultad de Quimica, Bioquimica y Farmacia, Universidad 
      Nacional de San Luis, San Luis, Argentina.
FAU - Silva, Juan Eduardo
AU  - Silva JE
AD  - Division de Inmunologia, Facultad de Quimica, Bioquimica y Farmacia, Universidad 
      Nacional de San Luis, San Luis, Argentina.
AD  - Instituto Multidisciplinario de Investigaciones Biologicas (IMIBIO), Consejo 
      Nacional de Investigaciones Cientificas y Tecnicas (CONICET), San Luis, 
      Argentina.
FAU - Gorlino, Carolina Virginia
AU  - Gorlino CV
AD  - Division de Inmunologia, Facultad de Quimica, Bioquimica y Farmacia, Universidad 
      Nacional de San Luis, San Luis, Argentina.
FAU - Arias, Jose Luis
AU  - Arias JL
AD  - Division de Inmunologia, Facultad de Quimica, Bioquimica y Farmacia, Universidad 
      Nacional de San Luis, San Luis, Argentina.
FAU - Beron, Walter
AU  - Beron W
AD  - Instituto de Histologia y Embriologia, Facultad de Ciencias Medicas, Universidad 
      Nacional de Cuyo - CONICET, Mendoza, Argentina.
FAU - Di Genaro, Maria Silvia
AU  - Di Genaro MS
AUID- ORCID: 0000-0001-9854-5786
AD  - Division de Inmunologia, Facultad de Quimica, Bioquimica y Farmacia, Universidad 
      Nacional de San Luis, San Luis, Argentina.
AD  - Instituto Multidisciplinario de Investigaciones Biologicas (IMIBIO), Consejo 
      Nacional de Investigaciones Cientificas y Tecnicas (CONICET), San Luis, 
      Argentina.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180301
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Interleukin-12 Subunit p40)
RN  - 0 (PHB2 protein, human)
RN  - 0 (Prohibitins)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor Decoy Receptors)
RN  - 1IEO802L3J (recombinant human tumor necrosis factor-binding protein-1)
SB  - IM
MH  - Animals
MH  - Arthritis, Reactive/*immunology/pathology
MH  - Cell Line
MH  - Cell Polarity
MH  - Coculture Techniques
MH  - Dendritic Cells/*immunology
MH  - Disease Models, Animal
MH  - Humans
MH  - Interleukin-12 Subunit p40/*metabolism
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - Mice, Knockout
MH  - Prohibitins
MH  - Receptors, Tumor Necrosis Factor, Type I/*genetics
MH  - Spleen/immunology
MH  - Th1 Cells/*cytology
MH  - Th17 Cells/*cytology
MH  - Tumor Necrosis Factor Decoy Receptors/*genetics
MH  - Yersinia Infections/*complications/immunology
MH  - Yersinia enterocolitica/*immunology
PMC - PMC5832265
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2018/03/02 06:00
MHDA- 2018/07/03 06:00
PMCR- 2018/03/01
CRDT- 2018/03/02 06:00
PHST- 2017/08/31 00:00 [received]
PHST- 2018/02/14 00:00 [accepted]
PHST- 2018/03/02 06:00 [entrez]
PHST- 2018/03/02 06:00 [pubmed]
PHST- 2018/07/03 06:00 [medline]
PHST- 2018/03/01 00:00 [pmc-release]
AID - PONE-D-17-32078 [pii]
AID - 10.1371/journal.pone.0193573 [doi]
PST - epublish
SO  - PLoS One. 2018 Mar 1;13(3):e0193573. doi: 10.1371/journal.pone.0193573. 
      eCollection 2018.