Article
Cell Biology
Xiaofen Liu, Wenjuan Zhang, Changbin Jing, Lei Gao, Cong Fu, Chunguang Ren, Yimei Hao, Mengye Cao, Ke Ma, Weijun Pan, Dantong Li
Summary: This study identified a novel zebrafish mutant line with a mutation in the Gemin5 gene, leading to specific deficiency in definitive hematopoiesis, which was attributed to impaired proliferation of HSPCs. The results suggest that Gemin5 plays an essential role in regulating HSPCs proliferation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Melanie Aureal, Irma Machuca-Gayet, Fabienne Coury
Summary: Rheumatoid arthritis is characterized by chronic synovial inflammation and irreversible bone erosions. Osteoclast-mediated bone resorption is the main cause of articular bone erosions, with autoantibodies, pro-inflammatory cytokines, and other regulating factors playing important roles in this process.
Review
Immunology
Francisco Caiado, Eric M. Pietras, Markus G. Manz
Summary: Inflammation is a defense response to infection or tissue damage involving activation and consumption of immune cells. Hematopoietic stem cells are influenced by inflammatory cues, replacing mature immune cells as needed. Lifelong inflammatory exposure contributes to HSC aging and the selection of premalignant HSC clones.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Rheumatology
Richard A. Furie, Gustavo Aroca, Matthew D. Cascino, Jay P. Garg, Brad H. Rovin, Analia Alvarez, Hilda Fragoso-Loyo, Elizabeth Zuta-Santillan, Thomas Schindler, Paul Brunetta, Cary M. Looney, Imran Hassan, Ana Malvar
Summary: This study compared the efficacy of obinutuzumab with standard therapies and placebo in the treatment of LN. The results showed that obinutuzumab achieved better complete renal responses at 52 and 104 weeks compared to standard therapies alone. It also showed improvements in other renal response measures, serologies, estimated glomerular filtration rate and proteinuria. Obinutuzumab was well tolerated and no new safety signals were identified.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Medicine, General & Internal
Hiroko Hashimoto, Shimpei Hashimoto, Yoshihiro Shimazaki
Summary: The study revealed that RA patients with fewer teeth were more likely to receive stronger RA therapies, independent of RA severity and other factors.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Oncology
Li Zheng, Cong Pan, Wanli Tian, Cailing Liang, Yunyu Feng, Wei He, Zirong Yang, Bochuan Wang, Qiang Qiu, Ning Li, Yuanyuan Sun, Huandi Qiu, Klarke M. Sample, Lingyun Zhou, Xianjun Zhu, Yiguo Hu
Summary: In this study, the role of Atp8a1 in hematopoiesis and HSCs was identified. Atp8a1 deletion resulted in the loss of phosphatidylserine asymmetry and chaos in intracellular signal transduction, which affected hematopoiesis and HSC function.
Article
Cell Biology
Jonas Nogueira Ferreira Maciel Gusmao, Khetyma Moreira Fonseca, Bruno Sousa Pinto Ferreira, Bruno Wesley de Freitas Alves, Howard Lopes Ribeiro Junior, Mario Roberto Pontes Lisboa, Karuza Maria Alves Pereira, Mariana Lima Vale, Delane Viana Gondim
Summary: Electroacupuncture (EA) has shown anti-inflammatory and anti-resorptive effects in experimental studies. In this rat study involving periodontitis and rheumatoid arthritis (RA), EA reduced pain intensity and inflammation related to periodontitis in arthritic rats, but did not prevent alveolar bone loss (ABL). EA was more effective in reducing ABL and bone radiographic density (BRD) in the presence of periodontitis.
Article
Immunology
Ting-Kuo Chang, You-Han Zhong, Shan-Chi Liu, Chien-Chung Huang, Chun-Hao Tsai, Hsiang-Ping Lee, Shih-Wei Wang, Chin-Jung Hsu, Chih-Hsin Tang
Summary: APLN treatment in RA synovial fibroblasts was found to increase Ang1 expression, promoting EPC angiogenesis, making APLN a novel therapeutic target for RA. Levels of APLN and Ang1 in synovial fluid from RA patients were significantly higher compared to those with osteoarthritis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Rheumatology
Gee Hee Kim, Yune-Jung Park
Summary: The incidence of diastolic dysfunction is higher in patients with rheumatoid arthritis, especially in the 30-49 age group. High CRP levels in RA patients are independently associated with DD. Early screening of myocardial function in premenopausal women with RA is important for preventing future cardiovascular disease.
ARTHRITIS RESEARCH & THERAPY
(2021)
Article
Medicine, General & Internal
Gerhard Schmalz, Markus Bartl, Jan Schmickler, Susann Patschan, Daniel Patschan, Dirk Ziebolz
Summary: This cross-sectional study aimed to investigate the potential associations between periodontal inflamed surface area (PISA) and tooth loss with disease-related parameters in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients. The study found that tooth loss is associated with disease activity, especially in RA individuals, while no associations were found between PISA and disease-related parameters in both groups.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Xiang Li, Xiaonan Tang, Yufei Wang, Changwei Chai, Zhehui Zhao, Haijing Zhang, Ying Peng, Lianqiu Wu
Summary: CS-semi5 showed positive effects on collagen-induced arthritis in mice, alleviating main pathologies and reducing inflammation and bone loss through NF-kappa B deactivation.
CS-semi5 treatment decreased TNF-alpha and IL-1 beta production in activated macrophages and inhibited osteoclast differentiation from macrophages.
Therefore, CS-semi5 may effectively ameliorate symptoms of rheumatoid arthritis by modulating the immune pathway.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Rheumatology
J. Ramirez, A. B. Azuaga-Pinango, B. Frade-Sosa, R. Gumucio-Sanguino, K. Cajiao-Sanchez, A. M. Cuervo, R. Celis, J. A. Narvaez, V Ruiz-Esquide, R. Castellanos-Moreira, A. Ponce, J. A. Gomez-Puerta, J. L. Pablos, R. Sanmarti, J. D. Canete
Summary: In patients with rheumatoid arthritis (RA), ultrasound proliferative synovitis (US PS) is associated with ACPA positivity, erosive disease, and a greater likelihood of needing to change disease-modifying anti-rheumatic drug therapy in the long-term. At the synovial level, this ultrasound pattern is characterized by higher vessel density.
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Klara Komici, Angelica Perna, Aldo Rocca, Leonardo Bencivenga, Giuseppe Rengo, Germano Guerra
Summary: Rheumatoid Arthritis is a chronic autoimmune inflammatory disease that can lead to endothelial damage and dysfunction. Endothelial Progenitor Cells play a crucial role in vascular homeostasis and repair, but there are conflicting results regarding their number and function in RA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Yumi Tsuchida, Yasuo Nagafuchi, Tomoko Uehara, Hisato Suzuki, Mamiko Yamada, Masanori Kono, Hiroaki Hatano, Hirofumi Shoda, Keishi Fujio, Kenjiro Kosaki
Summary: We report a patient with RA who has compound heterozygous variants in the COL11A2 gene. Autoantibodies against type XI collagen are detected in the sera of RA patients, suggesting a potential involvement of type XI collagen in the pathogenesis of RA. The hearing loss and osteoarthritis in this patient may be attributed to the compound heterozygous variants in the COL11A2 gene, and the conformational changes induced by these variants may have altered the immunogenicity of type XI collagen, leading to the development of RA.
Review
Biology
Diana Popescu, Elena Rezus, Minerva Codruta Badescu, Nicoleta Dima, Petronela Nicoleta Seritean Isac, Ioan-Teodor Dragoi, Ciprian Rezus
Summary: Rheumatoid arthritis (RA) is an independent cardiovascular risk factor and is associated with traditional risk factors such as smoking, arterial hypertension, dyslipidemia, insulin resistance, and obesity. Recent studies have identified markers like serum homocysteine, asymmetric dimethylarginine, or carotid intima-media thickness (cIMT) as predictors of cardiovascular risk in RA. Although the introduction of biological therapy has brought new perspectives, early detection of atherosclerosis and targeted therapies are crucial for reducing cardiovascular risk in RA patients.
Review
Immunology
Andrea D. Gloor, Gerald J. Berry, Jorg J. Goronzy, Cornelia M. Weyand
Summary: Giant cell arteritis and Takayasu arteritis are autoimmune and autoinflammatory vasculitides that are associated with age and show differences in pathogenesis and immunopathology.
SEMINARS IN IMMUNOPATHOLOGY
(2022)
Article
Medicine, Research & Experimental
Fengqin Fang, Wenqiang Cao, Yunmei Mu, Hirohisa Okuyama, Lingjie Li, Jingtao Qiu, Cornelia M. Weyand, Jorg J. Goronzy
Summary: CD39 serves as a checkpoint in purinergic signaling on effector T cells, affecting memory cell development and T cell immunity. The STAT6 pathway represses CD39 expression by inducing a transcription factor network, while inhibiting STAT6 increases CD39 expression and impairs T cell effector functions.
Article
Multidisciplinary Sciences
Masao Hashimoto, Koichi Araki, Maria A. Cardenas, Peng Li, Rohit R. Jadhav, Haydn T. Kissick, William H. Hudson, Donald J. McGuire, Rebecca C. Obeng, Andreas Wieland, Judong Lee, Daniel T. McManus, James L. Ross, Se Jin Im, Junghwa Lee, Jian-Xin Lin, Bin Hu, Erin E. West, Christopher D. Scharer, Gordon J. Freeman, Arlene H. Sharpe, Suresh S. Ramalingam, Alex Pellerin, Volker Teichgraber, William J. Greenleaf, Christian Klein, Jorg J. Goronzy, Pablo Umana, Warren J. Leonard, Kendall A. Smith, Rafi Ahmed
Summary: The study showed that combination therapy with PD-1 blockade and IL-2 during chronic lymphocytic choriomeningitis virus infection significantly alters the differentiation program of CD8(+) T cells, resulting in the generation of highly functional effector CD8(+) T cells that mediate viral control, thus providing a new perspective for cancer treatment.
Review
Cardiac & Cardiovascular Systems
Cornelia M. Weyand, Joerg J. Goronzy
Summary: Giant cell arteritis is an autoimmune disease that affects medium and large arteries, causing inflammation, obstruction, and aneurysm formation. The disease progresses through various steps, involving both innate and adaptive immune responses, leading to the infiltration of immune cells into the arterial wall and the development of tissue-damaging macrophages. Understanding these immune mechanisms provides opportunities for prevention and management of this devastating disease.
CIRCULATION RESEARCH
(2023)
Review
Immunology
Cornelia M. Weyand, Bowen Wu, Tao Huang, Zhaolan Hu, Jorg J. Goronzy
Summary: Mitochondria play crucial roles in cell metabolism, cell death pathways, cytoplasmic signaling networks, cellular stress responses, and nuclear gene expression. They are particularly important for immune cells, as they are involved in immune responses, autoimmunity, and tissue inflammation. Dysfunction in mitochondria has been linked to the development and progression of rheumatoid arthritis, affecting T cells during different stages of the disease.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
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)
Article
Immunology
Huimin Zhang, Rohit R. Jadhav, Wenqiang Cao, Isabel N. Goronzy, Tuantuan V. Zhao, Jun Jin, Shozo Ohtsuki, Zhaolan Hu, Jose Morales, William J. Greenleaf, Cornelia M. Weyand, Jorg J. Goronzy
Summary: Immune aging is a combination of cellular defects and low-inflammatory state. TCR activation in older adults accelerates remodeling of the epigenome and induces transcription factor networks favoring effector cell differentiation. Reduced HELIOS expression directs T cell fate decisions toward inflammatory effector cells that infiltrate tissue in older adults.
Article
Cell Biology
Luis I. Prieto, Ines Sturmlechner, Jorg J. Goronzy, Darren J. Baker
Summary: Harnessing the immunogenic potential of senescent cells can enhance antitumor immunity in certain contexts.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Wenqiang Cao, Ines Sturmlechner, Huimin Zhang, Jun Jin, Bin Hu, Rohit R. Jadhav, Fengqin Fang, Cornelia M. Weyand, Jorg J. Goronzy
Summary: Naive CD4+ T cells are more resistant to age-related loss than naive CD8+ T cells, indicating the presence of mechanisms that preferentially protect naive CD4+ T cells during aging. The study reveals that TRIB2 is more abundant in naive CD4+ T cells and suppresses AKT activation to prevent quiescence exit. Loss of TRIB2 leads to increased AKT activity, accelerated proliferation, and differentiation in response to IL-7. Transcription of TRIB2 is controlled by lineage-determining transcription factors ThPOK and RUNX3. Deletion of Zbtb7b (encoding ThPOK) and Cbfb (obligatory RUNT cofactor) attenuates the difference in lymphopenia-induced proliferation between naive CD4+ and CD8+ cells. In older adults, decreased expression of ThPOK and TRIB2 in naive CD4+ T cells causes loss of naivety. These findings highlight the importance of TRIB2 in regulating T cell homeostasis and provide insights into the differential resilience of CD8+ T cells to age-related changes.
Article
Cell Biology
Shozo Ohtsuki, Chenyao Wang, Ryu Watanabe, Hui Zhang, Mitsuhiro Akiyama, Melanie C. Bois, Joseph J. Maleszewski, Kenneth J. Warrington, Gerald J. Berry, Jorg J. Goronzy, Cornelia M. Weyand
Summary: Loss of function of inhibitory immune checkpoints can lead to autoimmune disease, such as giant cell arteritis (GCA). In this study, a defective CD155-CD96 immune checkpoint was found in GCA patients, resulting in the retention of CD155 in the endoplasmic reticulum (ER) of macrophages. Antigen-presenting cells with low CD155 expression induced the expansion of tissue invasive CD4+CD96+ T cells that released interleukin-9 (IL-9). The dysregulated immune response caused vessel wall destruction, which could be suppressed by anti-IL-9 antibodies in a GCA mouse model.
CELL REPORTS MEDICINE
(2023)
Review
Immunology
Yanyan Zheng, Qingxiang Liu, Jorg J. Goronzy, Cornelia M. Weyand
Summary: Evidence suggests that immune aging is one of the mechanisms leading to autoimmunity. Older adults have compromised immune responses but accumulate aged T cells, B cells, and myeloid cells. These changes can contribute to the development of autoimmune diseases through chronic inflammation and tissue damage. Dysfunctional mitochondria and lysosomes play a role in driving pathogenic T cells and macrophages in diseases like rheumatoid arthritis and giant cell arteritis. Recognizing immune aging as a risk factor for autoimmunity can lead to new immunomodulatory therapies targeting malfunctioning mitochondria and lysosomes.
SEMINARS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Jun Jin, Yunmei Mu, Huimin Zhang, Ines Sturmlechner, Chenyao Wang, Rohit R. Jadhav, Qiong Xia, Cornelia M. Weyand, Jorg J. Goronzy
Summary: In older adults, T cells contribute to chronic inflammation by releasing mtDNA due to increased expression of CISH. CISH targets an essential component of V-ATPase for degradation, impairing lysosomal function and leading to amphisomal release. Silencing CISH in older adults' T cells restores lysosomal activity and reduces inflammatory response.
Article
Geriatrics & Gerontology
Simon Lambert, Wenqiang Cao, Huimin Zhang, Alex Colville, Jie-Yu Liu, Cornelia M. Weyand, Jorg J. Goronzy, Claire E. Gustafson
Summary: The authors developed a lymphoid organoid system to maintain resting naïve T cells and conducted a deep phenotypic characterization of naïve T cells across ages, identifying reduced CD45RA density as a hallmark of aging. They suggest that external influences within the lymph node microenvironment may cause phenotypic conversion of naïve T cells in older adults.
FRONTIERS IN AGING
(2022)
Article
Endocrinology & Metabolism
Zhaolan Hu, Tuantuan Zhao, Tao Huang, Shozo Ohtsuki, Ke Jin, Isabel N. Goronzy, Bowen Wu, Matthew P. Abdel, Jacob W. Bettencourt, Gerald J. Berry, Jorg J. Goronzy, Cornelia M. Weyand
Summary: Hu and Zhao et al. have discovered a mechanism by which tissue macrophages in autoimmune diseases adapt to nutrient stress. This mechanism involves the cytokine CCL18 and the transcription factor RFX5, which regulate metabolic adaptation and antigen-presenting function in tissue inflammation.
Review
Geriatrics & Gerontology
Tuantuan V. Zhao, Yuki Sato, Jorg J. Goronzy, Cornelia M. Weyand
Summary: Aging of the immune system leads to a decline in host protection against cancer and infection. T cell aging is associated with the accumulation of aging-related phenotypes, some of which contribute to tissue inflammation in autoimmune diseases. Recent studies have shown that T cell aging is a risk factor for autoimmune diseases and is directly linked to the breakdown of T cell tolerance and tissue inflammation.
FRONTIERS IN AGING
(2022)