TDO2-overexpressed Dendritic Cells Possess Tolerogenicity and Ameliorate Collagen-induced Arthritis by Modulating the Th17/Regulatory T Cell Balance

被引：4

作者：

Jia, Chengyan ^{[1
]}

Wang, Yueye ^{[1
]}

Wang, Yi ^{[1
]}

Cheng, Meng ^{[1
]}

Dong, Weibo ^{[1
]}

Wei, Wei ^{[1
]}

Zhao, Yingjie ^{[1
,2
]}

Chang, Yan ^{[1
]}

机构：

[1] Anhui Med Univ, Anhui Collaborat Innovat Ctr Antiinflammatory & Im, Key Lab Antiinflammatory & Immune Med, Inst Clin Pharmacol,Minist Educ, Hefei 230601, Anhui, Peoples R China

[2] Anhui Med Univ, Affiliated Hosp 2, Dept Clin Pharmacol, Hefei, Peoples R China

来源：

JOURNAL OF IMMUNOLOGY | 2024年 / 212卷 / 06期

基金：

中国国家自然科学基金;

关键词：

ARYL-HYDROCARBON RECEPTOR; INDOLEAMINE 2,3-DIOXYGENASE; TRYPTOPHAN; KYNURENINE; TOLERANCE; SUPPRESSION; INHIBITION; EXPRESSION; PATHWAY; GLIOMA;

D O I：

10.4049/jimmunol.2300442

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Tolerogenic dendritic cells are promising for restoring immune homeostasis and may be an alternative therapy for autoimmune diseases such as rheumatoid arthritis. The kynurenine pathway is a vital mechanism that induces tolerance in dendritic cells (DCs). Tryptophan 2,3-dioxygenase (TDO2) is an important rate-limiting enzyme in the kynurenine pathway and participates in immune regulation. However, the role of TDO2 in shaping the tolerogenic phenotypes of DCs remains unclear. In this study, we investigated the effects and mechanisms of TDO2-overexpressed DCs in regulating the T cell balance both in vivo and in vitro. TDO2-overexpressed DC2.4 and TDO2-/- - / - mouse bone marrow- derived DCs (BMDCs) were generated to verify the role of TDO2 in DC maturation and functionality. TDO2 overexpression in BMDCs via PGE2 2 treatment exhibited an immature phenotype and tolerogenic state, whereas TDO2-/- - / - BMDCs exhibited a mature phenotype and a proinflammatory state. Furthermore, transplant of TDO2-overexpressed BMDCs alleviated collagen-induced arthritis severity in mice, which was correlated with a reduction in Th17 populations and an increase in regulatory T cells. Collectively, these results indicate that TDO2 plays an important role in the tolerogenic phenotype and may be a promising target for the generation tolerogenic DCs for rheumatoid arthritis treatment. The Journal of Immunology, 2024, 212: 941-950.- 950.

引用

页码：941 / 950

页数：11

共 43 条

[1] Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis [J].

Bell, G. M. ;

Anderson, A. E. ;

Diboll, J. ;

Reece, R. ;

Eltherington, O. ;

Harry, R. A. ;

Fouweather, T. ;

MacDonald, C. ;

Chadwick, T. ;

McColl, E. ;

Dunn, J. ;

Dickinson, A. M. ;

Hilkens, C. M. U. ;

Isaacs, John D. .

ANNALS OF THE RHEUMATIC DISEASES, 2017, 76 (01) :227-234

[2] Kynurenine pathway enzymes in dendritic cells initiate tolerogenesis in the absence of functional IDO [J].

Belladonna, Maria L. ;

Grohmann, Ursula ;

Guidetti, Paolo ;

Volpi, Claudia ;

Bianchi, Roberta ;

Fioretti, Maria C. ;

Schwarcz, Robert ;

Fallarino, Francesca ;

Puccetti, Paolo .

JOURNAL OF IMMUNOLOGY, 2006, 177 (01) :130-137

[3] Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients [J].

Benham, Helen ;

Nel, Hendrik J. ;

Law, Soi Cheng ;

Mehdi, Ahmed M. ;

Street, Shayna ;

Ramnoruth, Nishta ;

Pahau, Helen ;

Lee, Bernett T. ;

Ng, Jennifer ;

Brunck, Marion E. G. ;

Hyde, Claire ;

Trouw, Leendert A. ;

Dudek, Nadine L. ;

Purcell, Anthony W. ;

O'Sullivan, Brendan J. ;

Connolly, John E. ;

Paul, Sanjoy K. ;

Le Cao, Kim-Anh ;

Thomas, Ranjeny .

SCIENCE TRANSLATIONAL MEDICINE, 2015, 7 (290)

[4] Aryl hydrocarbon receptor control of a disease tolerance defence pathway [J].

Bessede, Alban ;

Gargaro, Marco ;

Pallotta, Maria T. ;

Matino, Davide ;

Servillo, Giuseppe ;

Brunacci, Cinzia ;

Bicciato, Silvio ;

Mazza, Emilia M. C. ;

Macchiarulo, Antonio ;

Vacca, Carmine ;

Iannitti, Rossana ;

Tissi, Luciana ;

Volpi, Claudia ;

Belladonna, Maria L. ;

Orabona, Ciriana ;

Bianchi, Roberta ;

Lanz, Tobias V. ;

Platten, Michael ;

Della Fazia, Maria A. ;

Piobbico, Danilo ;

Zelante, Teresa ;

Funakoshi, Hiroshi ;

Nakamura, Toshikazu ;

Gilot, David ;

Denison, Michael S. ;

Guillemin, Gilles J. ;

DuHadaway, James B. ;

Prendergast, George C. ;

Metz, Richard ;

Geffard, Michel ;

Boon, Louis ;

Pirro, Matteo ;

Iorio, Alfonso ;

Veyret, Bernard ;

Romani, Luigina ;

Grohmann, Ursula ;

Fallarino, Francesca ;

Puccetti, Paolo .

NATURE, 2014, 511 (7508) :184-+

[5] Therapeutic Effect of Exosomes From Indoleamine 2,3-Dioxygenase-Positive Dendritic Cells in Collagen-Induced Arthritis and Delayed-Type Hypersensitivity Disease Models [J].

Bianco, Nicole R. ;

Kim, Seon Hee ;

Ruffner, Melanie A. ;

Robbins, Paul D. .

ARTHRITIS AND RHEUMATISM, 2009, 60 (02) :380-389

[6] Targeting the IDO1/TDO2-KYN-AhR Pathway for Cancer Immunotherapy - Challenges and Opportunities [J].

Cheong, Jae Eun ;

Sun, Lijun .

TRENDS IN PHARMACOLOGICAL SCIENCES, 2018, 39 (03) :307-325

[7] Tryptophan catabolism generates autoimmune-preventive regulatory T cells [J].

Fallarino, Francesca ;

Grohmann, Ursula ;

You, Sylvaine ;

McGrath, Barbara C. ;

Cavener, Douglas R. ;

Vacca, Carmine ;

Orabona, Ciriana ;

Bianchi, Roberta ;

Belladonna, Maria L. ;

Volpi, Claudia ;

Fioretti, Maria C. ;

Puccetti, Paolo .

TRANSPLANT IMMUNOLOGY, 2006, 17 (01) :58-60

[8] The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor ζ-chain and induce a regulatory phenotype in naive T cells [J].

Fallarino, Francesca ;

Grohmann, Ursula ;

You, Sylvaine ;

McGrath, Barbara C. ;

Cavener, Douglas R. ;

Vacca, Carmine ;

Orabona, Ciriana ;

Bianchi, Roberta ;

Belladonna, Maria L. ;

Volpi, Claudia ;

Santamaria, Pere ;

Fioretti, Maria C. ;

Puccetti, Paolo .

JOURNAL OF IMMUNOLOGY, 2006, 176 (11) :6752-6761

[9] Indoleamine 2,3-dioxygenase 1 activation in mature cDC1 promotes tolerogenic education of inflammatory cDC2 via metabolic communication [J].

Gargaro, Marco ;

Scalisi, Giulia ;

Manni, Giorgia ;

Briseno, Carlos G. ;

Bagadia, Prachi ;

Durai, Vivek ;

Theisen, Derek J. ;

Kim, Sunkyung ;

Castelli, Marilena ;

Xu, Chenling A. ;

zu Horste, Gerd Meyer ;

Servillo, Giuseppe ;

Della Fazia, Maria A. ;

Mencarelli, Giulia ;

Ricciuti, Doriana ;

Padiglioni, Eleonora ;

Giacche, Nicola ;

Colliva, Carolina ;

Pellicciari, Roberto ;

Calvitti, Mario ;

Zelante, Teresa ;

Fuchs, Dietmar ;

Orabona, Ciriana ;

Boon, Louis ;

Bessede, Alban ;

Colonna, Marco ;

Puccetti, Paolo ;

Murphy, Theresa L. ;

Murphy, Kenneth M. ;

Fallarino, Francesca .

IMMUNITY, 2022, 55 (06) :1032-+

[10] Tolerance, DCs and tryptophan: much ado about IDO [J].

Grohmann, U ;

Fallarino, F ;

Puccetti, P .

TRENDS IN IMMUNOLOGY, 2003, 24 (05) :242-248

← 1 2 3 4 5 →