Review
Immunology
Qi Jiang, Guocan Yang, Qi Liu, Shengjun Wang, Dawei Cui
Summary: Rheumatoid arthritis is a systemic and heterogeneous autoimmune disease characterized by symmetrical polyarthritis, with dysfunction of regulatory T (Treg) cells potentially contributing to the breakdown of self-tolerance. The ideal treatment strategy for RA should focus on re-inducing self-tolerance to prevent obvious tissue injury.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Rheumatology
Achilleas Floudas, Nuno Neto, Carl Orr, Mary Canavan, Phil Gallagher, Conor Hurson, Michael G. Monaghan, Sunil Nagpar, Ronan H. Mullan, Douglas J. Veale, Ursula Fearon
Summary: This study investigates pathogenic and protective polyfunctional T-cell responses in patients with rheumatoid arthritis (RA), individuals at risk (IAR), and healthy controls (HC) synovial tissue biopsies, identifying a novel population of pathogenic polyfunctional T-cells enriched in RA joints prior to clinical inflammation. Results show increased plasticity of Tfh cells and CD4 T-cell polyfunctionality in RA patients, with enrichment of memory Treg cell responses. The switch from potentially protective to pathogenic T-cell polyfunctionality prior to clinical inflammation highlights a potential therapeutic intervention opportunity in RA.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Multidisciplinary Sciences
Dao X. Nguyen, Helen M. Baldwin, Amara N. Ezeonyeji, Mohammed Rohan Butt, Michael R. Ehrenstein
Summary: The study revealed that patients with PsA have an increased Th17:Treg ratio, which can be reversed by anti-TNF therapy. Treg from patients treated with different therapies showed contrasting effects on regulating effector T-cell migration, with TNF blockade boosting Treg suppression of migration.
Article
Health Care Sciences & Services
Amanda J. Eakin, Tahanver Ahmed, Cathy M. McGeough, Stephen Drain, H. Denis Alexander, Gary D. Wright, Philip Gardiner, Dawn Small, Anthony J. Bjourson, David S. Gibson
Summary: This study investigates the relationship between disease activity in rheumatoid arthritis (RA) and the numbers and phenotypes of circulating regulatory T cells (Tregs) and monocytes. It also explores the potential sialic acid link between Tregs and monocytes and the effects of sialic acid on Treg activation and cytokine release.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Immunology
Qingxiang Liu, Yanyan Zheng, Jorg J. Goronzy, Cornelia M. Weyand
Summary: Immune aging is a complex process that makes the host more susceptible to cancer, infection, and insufficient tissue repair. T cells, under extreme proliferative pressure, undergo genetic and epigenetic changes, lack mitochondrial fitness, and fail to maintain proteostasis, leading to a shift from host protection to host injury. Understanding T cell aging contributes to the knowledge of autoimmune conditions and provides opportunities for immunomodulatory therapy by restoring the intactness of aging T cells.
JOURNAL OF AUTOIMMUNITY
(2023)
Review
Immunology
Konstantin Kotschenreuther, Shuaifeng Yan, David M. Kofler
Summary: Regulatory T (T-reg) cells are crucial in the pathogenesis of rheumatoid arthritis (RA), contributing to immune homeostasis and tissue migration.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Xiaoya Li, Huihui Xu, Jing Huang, Dan Luo, Shuang Lv, Xiangchen Lu, Cheng Xiao
Summary: Regulatory T cells (Tregs) play a crucial role in promoting immune tolerance and maintaining immune system homeostasis. Dysfunction of Tregs is closely linked to rheumatoid arthritis (RA), and research on Tregs in RA has made significant progress in both basic and clinical aspects.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Isaac Narbona-Sanchez, Alba Perez-Linaza, Isabel Serrano-Garcia, Inmaculada Vico-Barranco, Luis M. Fernandez-Aguilar, Jose L. Poveda-Diaz, Maria J. Sanchez del Pino, Fermin Medina-Varo, Mikel M. Arbulo-Echevarria, Enrique Aguado
Summary: T lymphocytes play a crucial role in adaptive immune responses through recognition of peptide antigens via the T Cell Receptor (TCR). The expression of the adaptor molecule NTAL in T cells is associated with autoimmune disorders. In this study, the negative regulatory functions of NTAL in T cells were investigated using Jurkat cells as a T cell model. The results showed that NTAL expression decreased intracellular signals associated with TCR activation. Additionally, reduced NTAL expression was observed in CD4+ T cells from Rheumatoid Arthritis (RA) patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Juan He, Yu Li, Jian Chen, Qi Wu, Hongying Shan, Xiaocheng Wang, Miaomiao Zhang, Liping Nie, Qingwen Wang
Summary: Different subsets of CD8+ T cells are associated with clinical features and serological parameters in rheumatoid arthritis (RA). Naive CD8+ T cells are negatively correlated with disease activity, while CD8+ CD28-T cells and CD8+ CD27-T cells are positively correlated with disease activity. Activated CD8+ T cells and TCR gamma E+ CD8+ T cells may be involved in inflammation and lipid metabolism in RA.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alexandra A. Vita, Hend Aljobaily, David O. Lyons, Nicholas A. Pullen
Summary: The study demonstrates that berberine can delay the symptoms of collagen-induced arthritis and potentially mediate its effects through T cell suppression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Pooria Fazeli, Mehdi Kalani, Maryam Hosseini
Summary: Memory T cells are traditionally categorized into T central memory (T-CM) and T effector memory (T-EM) cells. However, a newly recognized subset called T memory stem cell (T-SCM) cells possesses characteristics of both T-CM and T-EM cells. These cells are capable of lymphoid homing and performing effector roles. T-SCM cells have stemness, antigen independency, high proliferative potential, signaling pathway, and lipid metabolism. This article reviews recent evidence on the functions of T-SCM cells in autoimmune disorders and introduces them as prognostic biomarkers and therapeutic targets.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Junxia Huang, Xinzhi Xu, Ji Yang
Summary: Th17 cells play a crucial role in the immune response against bacterial and fungal infections, but excessive IL-17 production can lead to immunopathology and inflammatory autoimmune diseases. Understanding the regulation of Th17 cells by miRNAs has enhanced our knowledge of their function in immune response and disease, including recent advances in miRNA-mediated dysregulation of Th17 cell fate in autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Pavel Shelyakin, Ksenia R. Lupyr, Evgeny S. Egorov, Ilya A. Kofiadi, Dmitriy B. Staroverov, Sofya A. Kasatskaya, Valeriia V. Kriukova, Irina A. Shagina, Ekaterina M. Merzlyak, Tatiana O. Nakonechnaya, Elena A. Latysheva, Irina A. Manto, Musa R. Khaitov, Sergey A. Lukyanov, Dmitriy M. Chudakov, Olga Britanova
Summary: The interplay between T- and B-cell compartments during naive, effector and memory T cell maturation is critical for a balanced immune response. Primary B-cell immunodeficiency arising from X-linked agammaglobulinemia (XLA) offers a model to explore B cell impact on T cell subsets, starting from the thymic selection. The findings suggest active B cell involvement in CD4 T cell subsets maturation, including B cell-dependent expansion of the naive Treg TCR repertoire that enables better control of self-reactive T cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Ulrika Norin, Carola Rintisch, Liesu Meng, Florian Forster, Diana Ekman, Jonatan Tuncel, Katrin Klocke, Johan Backlund, Min Yang, Michael Y. Bonner, Gonzalo Fernandez Lahore, Jaime James, Klementy Shchetynsky, Maria Bergquist, Inger Gjertsson, Norbert Hubner, Liselotte Backdahl, Rikard Holmdahl
Summary: The study demonstrates that mutation in the SH3gl1 gene and deficient expression of SH3GL1 protein are associated with the development of arthritis in rodents, providing complete protection from chronic autoimmune inflammatory disease. The findings suggest that SH3GL1 is a key regulator of T cell activation and could serve as a potential target for the treatment of autoimmune diseases like rheumatoid arthritis.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Marta Sanz, Brendan T. Mann, Paul L. Ryan, Alberto Bosque, Daniel J. Pennington, Holger Hackstein, Natalia Soriano-Sarabia
Summary: Under non-pathological conditions, human ?d T cells represent a small fraction of CD3(+) T cells in peripheral blood (1-10%). They constitute a unique subset of T lymphocytes that recognize stress ligands or non-peptide antigens through MHC-independent presentation. Major human ?d T cell subsets, Vd1 and Vd2, expand in response to microbial infection or malignancy, but possess distinct tissue localization, antigen recognition, and effector responses. By comparing highly purified Vd1 and Vd2 cells, this study found distinct genetic and phenotypic signatures that define functional differences in ?d T cell populations, suggesting that Vd1 and Vd2 T cells are different lineages. These findings will facilitate further investigation into the ligand specificity and unique role of Vd1 and Vd2 cells in early immune responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Keiji Hirota, Motomu Hashimoto, Yoshinaga Ito, Mayumi Matsuura, Hiromu Ito, Masao Tanaka, Hitomi Watanabe, Gen Kondoh, Atsushi Tanaka, Keiko Yasuda, Manfred Kopf, Alexandre J. Potocnik, Brigitta Stockinger, Noriko Sakaguchi, Shimon Sakaguchi
Article
Multidisciplinary Sciences
Lucas Ferrari de Andrade, Rong En Tay, Deng Pan, Adrienne M. Luoma, Yoshinaga Ito, Soumya Badrinath, Daphne Tsoucas, Bettina Franz, Kenneth F. May, Christopher J. Harvey, Sebastian Kobold, Jason W. Pyrdol, Charles Yoon, Guo-Cheng Yuan, F. Stephen Hodi, Glenn Dranoff, Kai W. Wucherpfennig
Article
Immunology
Yoshinaga Ito, Orr Ashenberg, Jason Pyrdol, Adrienne M. Luoma, Orit Rozenblatt-Rosen, Matan Hofree, Elena Christian, Lucas Ferrari de Andrade, Rong En Tay, Luc Teyton, Aviv Regev, Stephanie K. Dougan, Kai W. Wucherpfennig
JOURNAL OF EXPERIMENTAL MEDICINE
(2018)
Article
Multidisciplinary Sciences
Danbee Ha, Atsushi Tanaka, Tatsuya Kibayashi, Atsushi Tanemura, Daisuke Sugiyama, James Badger Wing, Ee Lyn Lim, Karen Wei Weng Teng, Dennis Adeegbe, Evan W. Newell, Ichiro Katayama, Hiroyoshi Nishikawa, Shimon Sakaguchi
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Review
Immunology
James B. Wing, Atsushi Tanaka, Shimon Sakaguchi
Article
Multidisciplinary Sciences
Takahiro Kamada, Yosuke Togashi, Christopher Tay, Danbee Ha, Akinori Sasaki, Yoshiaki Nakamura, Eiichi Sato, Shota Fukuoka, Yasuko Tada, Atsushi Tanaka, Hiromasa Morikawa, Akihito Kawazoe, Takahiro Kinoshita, Kohei Shitara, Shimon Sakaguchi, Hiroyoshi Nishikawa
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Review
Immunology
Atsushi Tanaka, Shimon Sakaguchi
EUROPEAN JOURNAL OF IMMUNOLOGY
(2019)
Article
Immunology
Atsushi Tanaka, Hiroyoshi Nishikawa, Shinsuke Noguchi, Daisuke Sugiyama, Hiromasa Morikawa, Yoshiko Takeuchi, Danbee Ha, Naoya Shigeta, Toshio Kitawaki, Yuka Maeda, Takuro Saito, Yoshinori Shinohara, Yoshihiro Kameoka, Keiko Iwaisako, Fumihiko Monma, Kohshi Ohishi, Julia Karbach, Elke Jaeger, Kenichi Sawada, Naoyuki Katayama, Naoto Takahashi, Shimon Sakaguchi
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Review
Immunology
Shimon Sakaguchi, Norihisa Mikami, James B. Wing, Atsushi Tanaka, Kenji Ichiyama, Naganari Ohkura
ANNUAL REVIEW OF IMMUNOLOGY, VOL 38
(2020)
Article
Immunology
Naganari Ohkura, Yoshiaki Yasumizu, Yohko Kitagawa, Atsushi Tanaka, Yamami Nakamura, Daisuke Motooka, Shota Nakamura, Yukinori Okada, Shimon Sakaguchi
Article
Immunology
Rong En Tay, Olamide Olawoyin, Paloma Cejas, Yingtian Xie, Clifford A. Meyer, Qing Yu Weng, David E. Fisher, Henry W. Long, Myles Brown, Hye-Jung Kim, Kai W. Wucherpfennig
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Article
Immunology
Naoya Shigeta, Keiichi Kumasawa, Atsushi Tanaka, James Badger Wing, Hitomi Nakamura, Shimon Sakaguchi, Tadashi Kimura
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2020)
Article
Multidisciplinary Sciences
Yujiro Kidani, Wataru Nogami, Yoshiaki Yasumizu, Atsunari Kawashima, Atsushi Tanaka, Yudai Sonoda, Yumi Tona, Kunitaka Nashiki, Reimi Matsumoto, Masaki Hagiwara, Motonao Osaki, Keiji Dohi, Takayuki Kanazawa, Azumi Ueyama, Mai Yoshikawa, Tetsuya Yoshida, Mitsunobu Matsumoto, Kanji Hojo, Satomi Shinonome, Hiroshi Yoshida, Michinari Hirata, Miya Haruna, Yamami Nakamura, Daisuke Motooka, Daisuke Okuzaki, Yasuko Sugiyama, Makoto Kinoshita, Tatsusada Okuno, Taigo Kato, Koji Hatano, Motohide Uemura, Ryoichi Imamura, Kazunori Yokoi, Atsushi Tanemura, Yasushi Shintani, Tadashi Kimura, Norio Nonomura, Hisashi Wada, Masaki Mori, Yuichiro Doki, Naganari Ohkura, Shimon Sakaguchi
Summary: Specific removal of clonally expanding Tregs in tumor tissues for a limited period by cell-depleting anti-CCR8 mAb treatment can generate potent tumor immunity without causing deleterious autoimmunity. This approach can induce memory-type tumor-specific effector T cells while avoiding severe autoimmune diseases, resulting in long-lasting tumor immunity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Atsushi Tanaka, Shinji Maeda, Takashi Nomura, Mara Anais Llamas-Covarrubias, Satoshi Tanaka, Lin Jin, Ee Lyn Lim, Hiromasa Morikawa, Yohko Kitagawa, Shuji Akizuki, Yoshinaga Ito, Chihiro Fujimori, Keiji Hirota, Tosei Murase, Motomu Hashimoto, Junichi Higo, Rose Zamoyska, Ryuzo Ueda, Daron M. M. Standley, Noriko Sakaguchi, Shimon Sakaguchi
Summary: This study investigates the relationship between aberrant TCR signaling and autoimmune disease, and provides a model to explain how altered TCR signaling triggers autoimmune diseases. The study found that reducing the expression of the ZAP-70 molecule to a critical range leads to the generation of autoimmune T cells and impairs the function of regulatory T cells, ultimately resulting in the occurrence of autoimmune/inflammatory diseases.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Oncology
Yoshinaga Ito, Deng Pan, Wubing Zhang, Xixi Zhang, Tiffany Y. Juan, Jason W. Pyrdol, Oleksandr Kyrysyuk, John G. Doench, X. Shirley Liu, Kai W. Wucherpfennig
Summary: Tumor heterogeneity is a major obstacle in cancer therapy, including immunotherapy. By targeting autophagy and TNF signaling pathways, MHC-I-deficient tumor cells can be sensitized to T cell-mediated apoptosis. Antigens from apoptotic MHC-I-deficient tumor cells can be efficiently cross-presented by dendritic cells, leading to increased infiltration of T cells producing IFN-γ and TNF-α. Targeting both pathways enables T cell-mediated elimination of tumors with a substantial population of resistant, MHC-I-deficient cells.