Article
Immunology
Yu Gao, Ruining Liu, Chenfei He, Juan Basile, Mattias Vesterlund, Marie Wahren-Herlenius, Alexander Espinoza, Cassandra Hokka-Zakrisson, Fahad Zadjali, Akihiko Yoshimura, Mikael Karlsson, Berit Carow, Martin E. Rottenberg
Summary: SOCS3 is a critical regulator of immune responses and inflammation, with its expression in thymic stromal cells being essential for T cell development and maintenance of thymus architecture. The inhibition of SOCS3 led to impaired thymocyte differentiation, proliferation, and increased apoptosis at different cell stages, ultimately affecting the generation of recent thymic emigrants in peripheral organs. The interaction between SOCS3 in thymic epithelial cells and TRIM 21 had significant implications for thymic cellularity and gene expression related to T cell selection and lympho-stromal interactions.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Daniel F. Zegarra-Ruiz, Dasom V. Kim, Kendra Norwood, Myunghoo Kim, Wan-Jung H. Wu, Fatima B. Saldana-Morales, Andrea A. Hill, Shubhabrata Majumdar, Stephanie Orozco, Rickesha Bell, June L. Round, Randy S. Longman, Takeshi Egawa, Matthew L. Bettini, Gretchen E. Diehl
Summary: Humans and their microbiota have a mutually beneficial relationship, where microbiota provides nutritional benefits and protection, and humans provide a hospitable environment. Maintaining this relationship requires immune balance to contain commensal microorganisms and limit inflammatory responses. Intestinal microorganisms can be recognized by T cells with antigen-specificity.
Review
Immunology
Min Hu, Natasha M. Rogers, Jennifer Li, Geoff Y. Zhang, Yuan Min Wang, Karli Shaw, Philip J. O'Connell, Stephen Alexander
Summary: Tregs play a crucial role in kidney transplantation by limiting immune activation and potentially reducing the need for immunosuppression. Studies have shown their importance in improving allo-specific Treg function in both animal and human models.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Xiaoqing Chen, Xue Liu, Yichao Jiang, Ningshao Xia, Chao Liu, Wenxin Luo
Summary: Chronic hepatitis B virus (HBV) infection is a major public health challenge, with over 250 million people worldwide infected. Priming of naive HBV-specific CD8 T cells is hindered, and this is closely related to abnormalities in the complex immune microenvironment. In this article, we summarize recent progress in understanding the abnormal priming of HBV-specific CD8 T cells and discuss corresponding immunotherapies to facilitate their functional recovery. We also highlight the importance of balancing viral clearance and pathological liver injury induced by CD8 T-cell activation during drug development.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Daniel A. Michelson, Koji Hase, Tsuneyasu Kaisho, Christophe Benoist, Diane Mathis
Summary: Medullary thymic epithelial cells (mTECs) ectopically express thousands of peripheral-tissue antigens (PTAs), which drive deletion or phenotypic diversion of self-reactive immature T cells during thymic differentiation. Lineage-defining transcription factors (TFs) for distinct cell types are present in different mTEC subtypes, and these factors are essential for the accumulation of mimetic cells and the expression of PTAs, contributing to self-tolerance.
Article
Multidisciplinary Sciences
John B. Grigg, Arthi Shanmugavadivu, Tommy Regen, Christopher N. Parkhurst, Anees Ahmed, Ann M. Joseph, Michael Mazzucco, Konrad Gronke, Andreas Diefenbach, Gerard Eberl, Timothy Vartanian, Ari Waisman, Gregory F. Sonnenberg
Summary: This study identified an inflammatory population of group 3 innate lymphoid cells (ILC3s) that play a critical role in a mouse model of multiple sclerosis. These ILC3s stimulate myelin-specific T cells through antigen presentation, leading to T cell responses in the CNS and disease development.
Review
Immunology
Aikaterini Hatzioannou, Athina Boumpas, Miranta Papadopoulou, Iosif Papafragkos, Athina Varveri, Themis Alissafi, Panayotis Verginis
Summary: Treg cell plasticity plays a significant role in autoimmunity and cancer, characterized by loss of Foxp3 expression. It has great therapeutic potential through destabilizing Treg cells to promote anti-tumor immunity or enhancing Treg cell stability to attenuate chronic inflammation.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Natalia M. Krajewska, Remi Fiancette, Ye H. Oo
Summary: Immune-mediated cholangiopathies are characterized by the destruction of bile ducts, leading to liver inflammation and fibrosis. Regulatory T cells (Tregs) play a crucial role in these diseases, but their function can be impaired by the inflamed microenvironment. Mast cells (MCs) are also involved in the pathogenesis by releasing pro-inflammatory mediators. MCs can indirectly influence Treg function and there are also direct interactions between MCs and Tregs. Understanding the crosstalk between Tregs and MCs is important for the progression of autoimmune cholangiopathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Grainne Jameson, Cathal Harmon, Rhyla Mae Santiago, Diarmaid D. Houlihan, Tom K. Gallagher, Lydia Lynch, Mark W. Robinson, Cliona O'Farrelly
Summary: Liver-resident CD56(bright)CD16(-) natural killer (NK) cells may contribute to immune tolerance during liver transplantation. RNA sequencing revealed that these liver-resident NK cells upregulated genes associated tissue residency and expressed immune receptors capable of activating NK cells. Functional assays demonstrated that hepatic NK cells had cytotoxic effects on allogenic CD8(+) T cells, with CD8(+) T cells being more susceptible than CD4(+) T cells, and this cytotoxic response could be enhanced by an anti-CD160 agonist.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Vilma Urbonaviciute, Laura Romero-Castillo, Bingze Xu, Huqiao Luo, Nadine Schneider, Sylvia Weisse, Nhu-Nguyen Do, Ana Oliveira-Coelho, Gonzalo Fernandez Lahore, Taotao Li, Pierre Sabatier, Christian M. Beusch, Johan Viljanen, Roman A. Zubarev, Jan Kihlberg, Johan Baecklund, Harald Burkhardt, Rikard Holmdahl
Summary: The long-term goal is to find a vaccine for autoimmune diseases. It has been challenging to safely regulate the targeting of natural regulatory antigen. This study shows that the administration of exogenous MHC II protein binding a unique galactosylated COL2 peptide leads to the expansion of VISTA-positive regulatory T cells, resulting in potent suppression and protection against arthritis in mice. The tolerogenic approach described here may be a promising therapy for rheumatoid arthritis and autoimmune diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Immunology
Jason Cheung, Beata Zahorowska, Michael Suranyi, Jeffrey K. W. Wong, Jason Diep, Stephen T. T. Spicer, Nirupama D. D. Verma, Suzanne J. Hodgkinson, Bruce M. M. Hall
Summary: The immune response to an allograft can activate lymphocytes that cause rejection. The activation of T regulatory cells can reduce allograft rejection and induce immune tolerance. Activated T regulatory cells can be distinguished by various markers. A more detailed characterization of these cells may help reduce non-specific immunosuppression.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Ainsley Lockhart, Aubrey Reed, Tiago Rezende de Castro, Calvin Herman, Maria Cecilia Campos Canesso, Daniel Mucida
Summary: The intestinal immune system must tolerate food antigens to avoid allergy, a process requiring CD4(+) T cells. Combining antigenically defined diets with gnotobiotic models, the study shows that both food and microbiota have distinct effects on the profile and T cell receptor repertoire of intestinal CD4(+) T cells. The response of CD4(+) T cells to food is disrupted by inflammatory challenge, but protection against food allergy is associated with Treg clonal expansion and decreased proinflammatory gene expression.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
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
Multidisciplinary Sciences
Daniel A. Michelson, Christophe Benoist, Diane Mathis
Summary: Medullary thymic epithelial cells (mTECs) are crucial for T cell central tolerance. In addition to the transcription factor Aire, we found that mTECs express the inhibitory receptor CTLA-4. CTLA-4(+) mTECs have a distinct gene signature associated with antigen presentation and interferon-gamma signaling, complementing the role of Aire.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Prerana Muralidhara, Vanshika Sood, Vishnu Vinayak Ashok, Kushagra Bansal
Summary: Immunological tolerance is critical during pregnancy to protect the semi-allogeneic fetus from immune responses. Regulatory T cells (Tregs) accumulate at the placenta in the uterus during pregnancy and confer immunological tolerance at the maternal-fetal interface. Tregs play a role in supporting proper growth of the embryo during pregnancy and their dysfunction is associated with pregnancy-related complications. Tregs also have a similar role in tumor immunity by creating a tolerogenic system.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Rheumatology
Hiroki Furuya, Mikio Nakajima, Kei Ikeda, Kaito Nakamura, Hiroyuki Ohbe, Shotaro Aso, Ryosuke Kumazawa, Taro Iwamoto, Arifumi Iwata, Shunsuke Furuta, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga, Hiroshi Nakajima
Summary: This study aimed to investigate the prognosis, clinical course, and management of severe interstitial lung disease (ILD) associated with myositis. The results showed that despite aggressive interventions, the mortality rate of myositis-associated ILD patients requiring mechanical ventilation is extremely high, with a significantly higher mortality rate in patients with dermatomyositis (DM) compared to those with polymyositis (PM).
ARTHRITIS CARE & RESEARCH
(2022)
Article
Rheumatology
Fumihiko Ando, Katsuhiko Takabayashi, Shinsuke Fujita, Hiroshi Nakajima, Hideki Hanaoka, Takahiro Suzuki
Summary: This study investigated the seasonal changes in the use of biological disease-modifying antirheumatic drugs (bDMARDs) and methotrexate (MTX), and found that their use was highest in spring and lowest in winter. These seasonal changes are often overlooked in daily practice.
MODERN RHEUMATOLOGY
(2023)
Article
Rheumatology
Junya Suzuki, Shunsuke Furuta, Takahiro Sugiyama, Taro Iwamoto, Kei Ikeda, Kotaro Suzuki, Hiroshi Nakajima
Summary: This study retrospectively assessed the proportion of aPL positivity and its association with thrombotic risk in Japanese patients with AAV. The results showed that 33.3% of the patients were aPL-positive, and aPL positivity was associated with a higher incidence of thrombotic events. Multivariate analyses confirmed aPL positivity as a risk factor for thrombosis.
MODERN RHEUMATOLOGY
(2023)
Article
Allergy
Nozomi Nishimura, Masaya Yokota, Shunjiro Kurihara, Arifumi Iwata, Takahiro Kageyama, Takashi Ito, Aiko Saku, Yuko Maezawa, Koichi Hirose, Hiroshi Nakajima
Summary: This study reveals the important role of STAT3 in airway epithelial cells, which suppresses HDM-induced allergic airway inflammation by regulating lipid metabolism.
ALLERGOLOGY INTERNATIONAL
(2022)
Article
Immunology
Hiroyuki Kondo, Takahiro Kageyama, Shigeru Tanaka, Kunihiro Otsuka, Shin-ichi Tsukumo, Yoichi Mashimo, Yoshihiro Onouchi, Hiroshi Nakajima, Koji Yasutomo
Summary: Three weeks after receiving the BNT162b2 vaccine, females in the Japanese population showed a higher number and stronger function of memory CD8+ T cells compared to males. Memory precursor effector cells were more abundant in females, and their memory CD8+ T cells had stronger responses to S protein stimulation. These findings provide important insights into the sex differences in cellular immune responses to mRNA vaccination.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Analytical
Jun Akimoto, Hiroharu Kashiwagi, Nobuhiro Morishima, Sei Obuse, Takashi Isoshima, Takahiro Kageyama, Hiroshi Nakajima, Yoshihiro Ito
Summary: A rapid automatic diagnostic system for multiple SARS-CoV-2 mutant protein-specific antibodies was developed using a microarray with photoreactive polymers. The system showed high correlation with conventional enzyme-linked immunoassay or immunochromatography, and was successfully used for testing sera or blood from recovered patients and vaccinated individuals, with good detection efficiency for virus mutation.
ANALYTICAL SCIENCES
(2022)
Article
Infectious Diseases
Hidetoshi Igari, Haruna Asano, Shota Murata, Toshihiko Yoshida, Kenji Kawasaki, Takahiro Kageyama, Key Ikeda, Hiromi Koshikawa, Yoshio Okuda, Misao Urushihara, Hitoshi Chiba, Misuzu Yahaba, Toshibumi Taniguchi, Kazuyuki Matsushita, Ichiro Yoshino, Koutaro Yokote, Hiroshi Nakajima
Summary: Booster vaccination can increase antibody levels and reduce the risk of SARS-CoV-2 infection. Healthcare workers in COVID-19 wards and individuals aged 20-49 are more susceptible to infection.
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2022)
Article
Multidisciplinary Sciences
Chiaki Iwamura, Kiyoshi Hirahara, Masahiro Kiuchi, Sanae Ikehara, Kazuhiko Azuma, Tadanaga Shimada, Sachiko Kuriyama, Syota Ohki, Emiri Yamamoto, Yosuke Inaba, Yuki Shiko, Ami Aoki, Kota Kokubo, Rui Hirasawa, Takahisa Hishiya, Kaori Tsuji, Tetsutaro Nagaoka, Satoru Ishkawa, Akira Kojima, Haruki Mito, Ryota Hase, Yasunori Kasahara, Naohide Kuriyama, Tetsuya Tsukamoto, Sukeyuki Nakamura, Takashi Urushibara, Satoru Kaneda, Seiichiro Sakao, Minoru Tobiume, Yoshio Suzuki, Mitsuhiro Tsujiwaki, Terufumi Kubo, Tadashi Hasegawa, Hiroshi Nakase, Osamu Nishida, Kazuhisa Takahashi, Komei Baba, Yoko Iizumi, Toshiya Okazaki, Motoko Y. Kimura, Ichiro Yoshino, Hidetoshi Igari, Hiroshi Nakajima, Takuji Suzuki, Hideki Hanaoka, Taka-aki Nakada, Yuzuru Ikehara, Koutaro Yokote, Toshinori Nakayama
Summary: This study investigates the pathogenesis of vasculitis and immunothrombosis in COVID-19, finding that SARS-CoV-2 accumulates in pulmonary vessels and causes vasculitis and microthrombi formation. The amount of plasma Myl9 is correlated with disease severity, and measuring plasma Myl9 together with other markers allows for a more accurate prediction of disease severity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Letter
Infectious Diseases
Yoichi Mashimo, Keiko Yamazaki, Takahiro Kageyama, Shigeru Tanaka, Toshibumi Taniguchi, Kazuyuki Matsushita, Hidetoshi Igari, Hideki Hanaoka, Koutaro Yokote, Hiroshi Nakajima, Yoshihiro Onouchi
JOURNAL OF INFECTION
(2022)
Review
Rheumatology
Ryohei Ono, Togo Iwahana, Shuji Toriumi, Kaoruko Aoki, Hirotoshi Kato, Kodai Kato, Masahiro Yasui, Yuzuho Nakagawa, Shunsuke Furuta, Hiroshi Nakajima, Yoshio Kobayashi
Summary: This study reports a rare case of a 43-year-old female with fulminant myocarditis with adult-onset Still's disease (AOSD). The patient had refractory AOSD and cardiogenic shock with significantly elevated ferritin levels. The case was successfully treated with canakinumab and mechanical circulatory support. A review of previous cases shows that myocarditis may be an early complication of AOSD, and the severity of AOSD may correlate with the severity of myocarditis.
CLINICAL RHEUMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Kensuke Suga, Akira Suto, Shigeru Tanaka, Yutaka Sugawara, Takahiro Kageyama, Junichi Ishikawa, Yoshie Sanayama, Kei Ikeda, Shunsuke Furuta, Shin-Ichiro Kagami, Arifumi Iwata, Koichi Hirose, Kotaro Suzuki, Osamu Ohara, Hiroshi Nakajima
Summary: Methotrexate (MTX) is a common treatment for rheumatoid arthritis (RA) but its precise mechanisms of action remain unclear. In this study, DNA microarray analyses of CD4+ T cells in RA patients revealed that TP63, specifically its isoform TAp63, was downregulated after MTX treatment. TAp63 was highly expressed in Th17 cells and suppressed by MTX in vitro. Knockdown of TAp63 in mouse Th17 cells improved arthritis symptoms. Furthermore, TAp63 knockdown in CD4+ T cells promoted Foxp3 expression and enhanced the suppressive function of induced Treg cells. In summary, TAp63 suppresses Foxp3 expression and worsens autoimmune arthritis.
Article
Rheumatology
Kazuya Abe, Shunsuke Furuta, Yoshihisa Kobayashi, Takao Sugiyama, Shin-Ichiro Kagami, Daiki Nakagomi, Taro Iwamoto, Kei Ikeda, Hiroshi Nakajima
Summary: This study aimed to assess the association between spontaneous pneumomediastinum (SPNM) occurrence and mortality in myositis patients with interstitial lung disease (ILD) according to antimelanoma differentiation-associated gene 5 (MDA5) antibody status. The results showed that SPNM was more common in myositis patients who were anti-MDA5 antibody positive, and it was associated with a higher risk of mortality.
Article
Rheumatology
Koto Hattori, Shigeru Tanaka, Junichi Ishikawa, Yoko Yabe, Taro Iwamoto, Shunsuke Furuta, Kei Ikeda, Kotaro Suzuki, Hiroshi Nakajima
Summary: This case report describes a SLE patient who developed VD-VZV during hospitalization. The patient presented with vesicular eruption and subsequent testing confirmed VD-VZV infection.
MODERN RHEUMATOLOGY CASE REPORTS
(2023)
Article
Rheumatology
Jumpei Shoda, Shigeru Tanaka, Keishi Etori, Koto Hattori, Tadamichi Kasuya, Kei Ikeda, Yuko Maezawa, Akira Suto, Kotaro Suzuki, Junichi Nakamura, Yoshiro Maezawa, Minoru Takemoto, Christer Betsholtz, Koutaro Yokote, Seiji Ohtori, Hiroshi Nakajima
Summary: The expression of semaphorin 3G in CD4(+) T cells is downregulated by MTX treatment in patients with RA, while upregulation of semaphorin 3G in the RA synovium exacerbates joint inflammation through the accumulation of macrophages.
ARTHRITIS RESEARCH & THERAPY
(2022)
Article
Rheumatology
Takahiro Sugiyama, Shunsuke Furuta, Masaki Hiraguri, Kei Ikeda, Yosuke Inaba, Shin-Ichiro Kagami, Yasuhiko Kita, Kei Kobayashi, Yoshihisa Kobayashi, Kazuhiro Kurasawa, Daiki Nakagomi, Yasushi Nawata, Yohei Kawasaki, Yuki Shiko, Takao Sugiyama, Hiroshi Nakajima
Summary: This study identified two subgroups of Adult-onset Still's disease (AOSD): the typical group and the elderly-onset group. Although the survival of AOSD patients was generally good, they often experienced relapses. Age >= 65 years at disease onset was identified as a risk factor for relapse.
ARTHRITIS RESEARCH & THERAPY
(2022)