PMID- 27647832
OWN - NLM
STAT- MEDLINE
DCOM- 20170814
LR  - 20181113
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 197
IP  - 8
DP  - 2016 Oct 15
TI  - IDO1 and TGF-beta Mediate Protective Effects of IFN-alpha in Antigen-Induced Arthritis.
PG  - 3142-3151
AB  - IFN-alpha prevents Ag-induced arthritis (AIA), and in this study we investigated the 
      role of IDO1 and TGF-beta signaling for this anti-inflammatory property of IFN-alpha. 
      Arthritis was induced by methylated BSA (mBSA) in mBSA-sensitized wild-type (WT), 
      Ido1(-/-), or Ifnar(-/-) mice, treated or not with IFN-alpha or the IDO1 product 
      kynurenine (Kyn). Enzymatic IDO1 activity, TGF-beta, and plasmacytoid dendritic 
      cells (pDC) were neutralized by 1-methyltryptophan and Abs against TGF-beta and pDC, 
      respectively. IDO1 expression was determined by RT-PCR, Western blot, and FACS, 
      and enzymatic activity by HPLC. Proliferation was measured by (3)H-thymidine 
      incorporation and TGF-beta by RT-PCR and ELISA. WT but not Ido1(-/-) mice were 
      protected from AIA by IFN-alpha, and Kyn, the main IDO1 product, also prevented AIA, 
      both in WT and Ifnar(-/-) mice. Protective treatment with IFN-alpha increased the 
      expression of IDO1 in pDC during AIA, and Ab-mediated depletion of pDC, either 
      during mBSA sensitization or after triggering of arthritis, completely abrogated 
      the protective effect of IFN-alpha. IFN-alpha treatment also increased the enzymatic IDO1 
      activity (Kyn/tryptophan ratio), which in turn activated production of TGF-beta. 
      Neutralization of enzymatic IDO1 activity or TGF-beta signaling blocked the 
      protective effect of IFN-alpha against AIA, but only during sensitization and not 
      after triggering of arthritis. Likewise, inhibition of the IDO1 enzymatic 
      activity in the sensitization phase, but not after triggering of arthritis, 
      subdued the IFN-alpha-induced inhibition of mBSA-induced proliferation. In 
      conclusion, presence of IFN-alpha at Ag sensitization activates an 
      IDO1/TGF-beta-dependent anti-inflammatory program that upon antigenic rechallenge 
      prevents inflammation via pDC.
CI  - Copyright (c) 2016 by The American Association of Immunologists, Inc.
FAU - Chalise, Jaya Prakash
AU  - Chalise JP
AUID- ORCID: 0000-0001-6462-2819
AD  - Division of Rheumatology, Autoimmunity, and Immune Regulation, Department of 
      Clinical and Experimental Medicine, Linkoping University, Linkoping 58185, 
      Sweden; jaya.prakash.chalise@liu.se mattias.magnusson@liu.se.
FAU - Pallotta, Maria Teresa
AU  - Pallotta MT
AUID- ORCID: 0000-0002-0417-1638
AD  - Department of Experimental Medicine, University of Perugia, 06100 Perugia, Italy.
FAU - Narendra, Sudeep Chenna
AU  - Narendra SC
AD  - Division of Rheumatology, Autoimmunity, and Immune Regulation, Department of 
      Clinical and Experimental Medicine, Linkoping University, Linkoping 58185, 
      Sweden.
FAU - Carlsson, Bjorn
AU  - Carlsson B
AD  - Division of Drug Research, Clinical Pharmacology, Department of Medical and 
      Health Sciences, Linkoping University, Linkoping 58185, Sweden; and.
FAU - Iacono, Alberta
AU  - Iacono A
AUID- ORCID: 0000-0002-2650-072X
AD  - Department of Experimental Medicine, University of Perugia, 06100 Perugia, Italy.
FAU - Namale, Joanitah
AU  - Namale J
AD  - Division of Rheumatology, Autoimmunity, and Immune Regulation, Department of 
      Clinical and Experimental Medicine, Linkoping University, Linkoping 58185, 
      Sweden.
FAU - Boon, Louis
AU  - Boon L
AD  - EPIRUS Biopharmaceuticals Netherlands BV, 3584 CM Utrecht, the Netherlands.
FAU - Grohmann, Ursula
AU  - Grohmann U
AUID- ORCID: 0000-0001-7952-1850
AD  - Department of Experimental Medicine, University of Perugia, 06100 Perugia, Italy.
FAU - Magnusson, Mattias
AU  - Magnusson M
AUID- ORCID: 0000-0002-6565-4027
AD  - Division of Rheumatology, Autoimmunity, and Immune Regulation, Department of 
      Clinical and Experimental Medicine, Linkoping University, Linkoping 58185, 
      Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160919
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (IDO1 protein, mouse)
RN  - 0 (Ifnar1 protein, mouse)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Transforming Growth Factor beta)
RN  - 156986-95-7 (Receptor, Interferon alpha-beta)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - 343-65-7 (Kynurenine)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/*immunology
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Dendritic Cells/*physiology
MH  - Gene Expression Regulation
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/*metabolism
MH  - Kynurenine/administration & dosage
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Knockout
MH  - Receptor, Interferon alpha-beta/genetics/*metabolism
MH  - Serum Albumin, Bovine/immunology
MH  - Signal Transduction
MH  - Transforming Growth Factor beta/*metabolism
PMC - PMC5055200
EDAT- 2016/09/21 06:00
MHDA- 2017/08/15 06:00
PMCR- 2016/09/19
CRDT- 2016/09/21 06:00
PHST- 2015/10/02 00:00 [received]
PHST- 2016/08/21 00:00 [accepted]
PHST- 2016/09/21 06:00 [pubmed]
PHST- 2017/08/15 06:00 [medline]
PHST- 2016/09/21 06:00 [entrez]
PHST- 2016/09/19 00:00 [pmc-release]
AID - jimmunol.1502125 [pii]
AID - ji_1502125 [pii]
AID - 10.4049/jimmunol.1502125 [doi]
PST - ppublish
SO  - J Immunol. 2016 Oct 15;197(8):3142-3151. doi: 10.4049/jimmunol.1502125. Epub 2016 
      Sep 19.