Cargando…

Interferon Gamma Suppresses Collagen-Induced Arthritis by Regulation of Th17 through the Induction of Indoleamine-2,3-Deoxygenase

C57BL/6 mice are known to be resistant to the development of collagen-induced arthritis (CIA). However, they show a severe arthritic phenotype when the Ifng gene is deleted. Although it has been proposed that IFN-γ suppresses inflammation in CIA via suppressing Th17 which is involved in the pathogen...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Jaeseon, Lee, Jennifer, Park, Mi-Kyung, Lim, Mi-Ae, Park, Eun-Mi, Kim, Eun-kyung, Yang, Eun-Ji, Lee, Seon-Yeong, Jhun, Joo-Yeon, Park, Sung-Hwan, Kim, Ho-Youn, Cho, Mi-La
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3628800/
https://www.ncbi.nlm.nih.gov/pubmed/23613752
http://dx.doi.org/10.1371/journal.pone.0060900
_version_ 1782266467026206720
author Lee, Jaeseon
Lee, Jennifer
Park, Mi-Kyung
Lim, Mi-Ae
Park, Eun-Mi
Kim, Eun-kyung
Yang, Eun-Ji
Lee, Seon-Yeong
Jhun, Joo-Yeon
Park, Sung-Hwan
Kim, Ho-Youn
Cho, Mi-La
author_facet Lee, Jaeseon
Lee, Jennifer
Park, Mi-Kyung
Lim, Mi-Ae
Park, Eun-Mi
Kim, Eun-kyung
Yang, Eun-Ji
Lee, Seon-Yeong
Jhun, Joo-Yeon
Park, Sung-Hwan
Kim, Ho-Youn
Cho, Mi-La
author_sort Lee, Jaeseon
collection PubMed
description C57BL/6 mice are known to be resistant to the development of collagen-induced arthritis (CIA). However, they show a severe arthritic phenotype when the Ifng gene is deleted. Although it has been proposed that IFN-γ suppresses inflammation in CIA via suppressing Th17 which is involved in the pathogenesis of CIA, the exact molecular mechanism of the Th17 regulation by IFN-γ is poorly understood. This study was conducted to 1) clarify that arthritogenic condition of IFN-γ knockout (KO) mice is dependent on the disinhibition of Th17 and 2) demonstrate that IFN-γ-induced indoleamine2,3dioxgenase (IDO) is engaged in the regulation of Th17. The results showed that the IFN-γ KO mice displayed increased levels of IL-17 producing T cells and the exacerbation of arthritis. Also, production of IL-17 by the splenocytes of the IFN-γ KO mice was increased when cultured with type II collagen. When Il17 was deleted from the IFN-γ KO mice, only mild arthritis developed without any progression of the arthritis score. The proportion of CD44(high)CD62L(low) memory-like T cells were elevated in the spleen, draining lymph node and mesenteric lymph node of IFN-γ KO CIA mice. Meanwhile, CD44(low)CD62L(high) naïve T cells were increased in IFN-γ and IL-17 double KO CIA mice. When Th17 polarized CD4+ T cells of IFN-γ KO mice were co-cultured with their own antigen presenting cells (APCs), a greater increase in IL-17 production was observed than in co-culture of the cells from wild type mice. In contrast, when APCs from IFN-γ KO mice were pretreated with IFN-γ, there was a significant reduction in IL-17 in the co-culture system. Of note, pretreatment of 1-methyl-DL- tryptophan, a specific inhibitor of IDO, abolished the inhibitory effects of IFN-γ. Given that IFN-γ is a potent inducer of IDO in APCs, these results suggest that IDO is involved in the regulation of IL-17 by IFN-γ.
format Online
Article
Text
id pubmed-3628800
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-36288002013-04-23 Interferon Gamma Suppresses Collagen-Induced Arthritis by Regulation of Th17 through the Induction of Indoleamine-2,3-Deoxygenase Lee, Jaeseon Lee, Jennifer Park, Mi-Kyung Lim, Mi-Ae Park, Eun-Mi Kim, Eun-kyung Yang, Eun-Ji Lee, Seon-Yeong Jhun, Joo-Yeon Park, Sung-Hwan Kim, Ho-Youn Cho, Mi-La PLoS One Research Article C57BL/6 mice are known to be resistant to the development of collagen-induced arthritis (CIA). However, they show a severe arthritic phenotype when the Ifng gene is deleted. Although it has been proposed that IFN-γ suppresses inflammation in CIA via suppressing Th17 which is involved in the pathogenesis of CIA, the exact molecular mechanism of the Th17 regulation by IFN-γ is poorly understood. This study was conducted to 1) clarify that arthritogenic condition of IFN-γ knockout (KO) mice is dependent on the disinhibition of Th17 and 2) demonstrate that IFN-γ-induced indoleamine2,3dioxgenase (IDO) is engaged in the regulation of Th17. The results showed that the IFN-γ KO mice displayed increased levels of IL-17 producing T cells and the exacerbation of arthritis. Also, production of IL-17 by the splenocytes of the IFN-γ KO mice was increased when cultured with type II collagen. When Il17 was deleted from the IFN-γ KO mice, only mild arthritis developed without any progression of the arthritis score. The proportion of CD44(high)CD62L(low) memory-like T cells were elevated in the spleen, draining lymph node and mesenteric lymph node of IFN-γ KO CIA mice. Meanwhile, CD44(low)CD62L(high) naïve T cells were increased in IFN-γ and IL-17 double KO CIA mice. When Th17 polarized CD4+ T cells of IFN-γ KO mice were co-cultured with their own antigen presenting cells (APCs), a greater increase in IL-17 production was observed than in co-culture of the cells from wild type mice. In contrast, when APCs from IFN-γ KO mice were pretreated with IFN-γ, there was a significant reduction in IL-17 in the co-culture system. Of note, pretreatment of 1-methyl-DL- tryptophan, a specific inhibitor of IDO, abolished the inhibitory effects of IFN-γ. Given that IFN-γ is a potent inducer of IDO in APCs, these results suggest that IDO is involved in the regulation of IL-17 by IFN-γ. Public Library of Science 2013-04-16 /pmc/articles/PMC3628800/ /pubmed/23613752 http://dx.doi.org/10.1371/journal.pone.0060900 Text en © 2013 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lee, Jaeseon
Lee, Jennifer
Park, Mi-Kyung
Lim, Mi-Ae
Park, Eun-Mi
Kim, Eun-kyung
Yang, Eun-Ji
Lee, Seon-Yeong
Jhun, Joo-Yeon
Park, Sung-Hwan
Kim, Ho-Youn
Cho, Mi-La
Interferon Gamma Suppresses Collagen-Induced Arthritis by Regulation of Th17 through the Induction of Indoleamine-2,3-Deoxygenase
title Interferon Gamma Suppresses Collagen-Induced Arthritis by Regulation of Th17 through the Induction of Indoleamine-2,3-Deoxygenase
title_full Interferon Gamma Suppresses Collagen-Induced Arthritis by Regulation of Th17 through the Induction of Indoleamine-2,3-Deoxygenase
title_fullStr Interferon Gamma Suppresses Collagen-Induced Arthritis by Regulation of Th17 through the Induction of Indoleamine-2,3-Deoxygenase
title_full_unstemmed Interferon Gamma Suppresses Collagen-Induced Arthritis by Regulation of Th17 through the Induction of Indoleamine-2,3-Deoxygenase
title_short Interferon Gamma Suppresses Collagen-Induced Arthritis by Regulation of Th17 through the Induction of Indoleamine-2,3-Deoxygenase
title_sort interferon gamma suppresses collagen-induced arthritis by regulation of th17 through the induction of indoleamine-2,3-deoxygenase
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3628800/
https://www.ncbi.nlm.nih.gov/pubmed/23613752
http://dx.doi.org/10.1371/journal.pone.0060900
work_keys_str_mv AT leejaeseon interferongammasuppressescollageninducedarthritisbyregulationofth17throughtheinductionofindoleamine23deoxygenase
AT leejennifer interferongammasuppressescollageninducedarthritisbyregulationofth17throughtheinductionofindoleamine23deoxygenase
AT parkmikyung interferongammasuppressescollageninducedarthritisbyregulationofth17throughtheinductionofindoleamine23deoxygenase
AT limmiae interferongammasuppressescollageninducedarthritisbyregulationofth17throughtheinductionofindoleamine23deoxygenase
AT parkeunmi interferongammasuppressescollageninducedarthritisbyregulationofth17throughtheinductionofindoleamine23deoxygenase
AT kimeunkyung interferongammasuppressescollageninducedarthritisbyregulationofth17throughtheinductionofindoleamine23deoxygenase
AT yangeunji interferongammasuppressescollageninducedarthritisbyregulationofth17throughtheinductionofindoleamine23deoxygenase
AT leeseonyeong interferongammasuppressescollageninducedarthritisbyregulationofth17throughtheinductionofindoleamine23deoxygenase
AT jhunjooyeon interferongammasuppressescollageninducedarthritisbyregulationofth17throughtheinductionofindoleamine23deoxygenase
AT parksunghwan interferongammasuppressescollageninducedarthritisbyregulationofth17throughtheinductionofindoleamine23deoxygenase
AT kimhoyoun interferongammasuppressescollageninducedarthritisbyregulationofth17throughtheinductionofindoleamine23deoxygenase
AT chomila interferongammasuppressescollageninducedarthritisbyregulationofth17throughtheinductionofindoleamine23deoxygenase