Review
Immunology
Ritesh Kumar, Arianne L. Theiss, K. Venuprasad
Summary: ROR gamma t plays a crucial role in regulating IL-17-driven inflammation through multiple post-translational modifications. Understanding these pathways is essential for studying the pathogenic role of ROR gamma t+IL-17+ cells and developing potential therapeutic strategies.
TRENDS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Mahesh Kathania, Ritesh Kumar, Elviche Taskem Lenou, Venkatesha Basrur, Arianne L. Theiss, Jonathan Chernoff, K. Venuprasad
Summary: Dysregulated interleukin-17 expression and its downstream signaling is strongly linked to inflammatory bowel diseases. We identified that Pak2 directly interacts with ROR gamma t and regulates its activity through phosphorylation.
Article
Immunology
Chun-Yu Lin, Chung-Hao Huang, Wen-Hung Wang, Jyrki Tenhunen, Ling-Chien Hung, Chi-Chou Lin, Yu-Cheng Chen, Yen-Hsu Chen, Wei-Ting Liao
Summary: Exposure to DEHP was associated with gastrointestinal bleeding in DV-infected patients, while MEHP treatment led to changes in macrophage immune responses and DV viral load. The study revealed a negative correlation between urine sigma DEHP levels and serum IL-23 levels in patients, highlighting the potential impact of environmental hormones on dengue disease outcomes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Ritu Sarin, Ran Gu, Zahra Jalali, Emanual Maverakis, Maria G. Tsokos, Iannis E. Adamopoulos
Summary: Interleukin 27 has both pro-inflammatory and anti-inflammatory properties in autoimmunity. The anti-inflammatory effects of IL-27 are linked with inhibition of Th17 differentiation and IL-27 also inhibits IL-23-induced inflammation associated with myeloid cell infiltration in the joints and spleen. The IL-27 anti-inflammatory response is associated with reduced levels of myeloid cells in the spleen and bone marrow.
CLINICAL IMMUNOLOGY
(2023)
Article
Engineering, Biomedical
Sjoukje J. C. van der Stegen, Pieter L. Lindenbergh, Roseanna M. Petrovic, Hongyao Xie, Mame P. Diop, Vera Alexeeva, Yuzhe Shi, Jorge Mansilla-Soto, Mohamad Hamieh, Justin Eyquem, Annalisa Cabriolu, Xiuyan Wang, Ramzey Abujarour, Tom Lee, Raedun Clarke, Bahram Valamehr, Maria Themeli, Isabelle Riviere, Michel Sadelain
Summary: This study demonstrates that delaying CAR expression and calibrating its signaling strength in induced pluripotent stem cells (iPSCs) can facilitate the generation of potent CAR T cells for immunotherapies, achieving effective tumor control in a mouse model.
NATURE BIOMEDICAL ENGINEERING
(2022)
Article
Multidisciplinary Sciences
Ayushi Verma, Akhilesh Singh, Manish Pratap Singh, Mushtaq Ahmad Nengroo, Krishan Kumar Saini, Saumya Ranjan Satrusal, Muqtada Ali Khan, Priyank Chaturvedi, Abhipsa Sinha, Sanjeev Meena, Anup Kumar Singh, Dipak Datta
Summary: The selective hyper-activation of functional EZH2 (H3K27me3) alters TNBC metastatic landscape and drives peritoneal metastasis, suggesting a potential role for trimethylation function of EZH2 in TNBC.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Fang Zhang, Ye Liu, Shiqi Wang, Xin Yan, Yue Lin, Deyan Chen, Qian Tan, Zhiwei Wu
Summary: In this study, we found that interleukin 25 (IL-25) can promote diabetic wound healing by mediating IL-17RB signaling. IL-25 improves angiogenesis and collagen deposition, thus improving the wound healing process. Additionally, IL-25 protects endothelial cells from high glucose damage, promoting cell migration and tube formation. This study provides a new therapeutic strategy for treating poor healing diabetic wounds.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Bhawna Yadav, Charles A. Specht, Chrono K. Lee, Maria Pokrovskii, Jun R. Huh, Dan R. Littman, Stuart M. Levitz
Summary: Exposure to mold, Aspergillus, is generally harmless to healthy individuals but can lead to invasive and allergic aspergillosis in immunocompromised and atopic individuals. In murine models of pulmonary aspergillosis, lung eosinophils express IL-17, ROR gamma t, and IL-23R. However, IL-23 is not necessary for the production of IL-17 and ROR gamma t in this context.
Article
Multidisciplinary Sciences
Lei Xu, Chuan Wei, Ying Chen, Yue Wu, Xiaoli Shou, Wenjie Chen, Di Lu, Haoran Sun, Wei Li, Beibei Yu, Xiaowei Wang, Xiaojun Zhang, Yanxiong Yu, Zhigang Lei, Rui Tang, Jifeng Zhu, Yalin Li, Linrong Lu, Hong Zhou, Sha Zhou, Chuan Su, Xiaojun Chen
Summary: Severe infection commonly leads to immunosuppression, impairing pathogen clearance and increasing susceptibility to secondary infection. This study uncovers the role of IL-33 in immunosuppression by inducing thymic involution-associated naive T cell dysfunction and disrupting T cell aging. The findings suggest that targeting IL-33 or ST2 may be a promising strategy to rejuvenate T cell immunity and better control severe infection.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Hao Li, Maria G. Tsokos, Rhea Bhargava, Iannis E. Adamopoulos, Hanni Menn-Josephy, Isaac E. Stillman, Philip Rosenstiel, Jarrat Jordan, George C. Tsokos
Summary: The study found that IL-23 can affect renal tubular epithelial cells by inhibiting the expression of IL-23 receptor, increasing the levels of free arginine, suppressing T cell proliferation, and inflammatory cytokine production. The results suggest that renal tubular epithelial cells play an immunosuppressive role in regulating kidney inflammation.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Immunology
Izumi Ohigashi, Melina Frantzeskakis, Alison Jacques, Sayumi Fujimori, Aya Ushio, Fusano Yamashita, Naozumi Ishimaru, Da Yin, Margaret Cam, Michael C. Kelly, Parirokh Awasthi, Kensuke Takada, Yousuke Takahama
Summary: The study revealed that the thymoproteasome plays a crucial role in the production of CD8(+) T cells, optimizing the cell development process. This finding indicates that the thymoproteasome regulates the formation of the TCR repertoire, playing a key role in the development of CD8(+) T cells.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Akansha M. Shah, Lei Guo, Maria Gabriela Morales, Priscilla Jaichander, Kenian Chen, Huocong Huang, Karla Cano Hernandez, Lin Xu, Rhonda Bassel-Duby, Eric N. Olson, Ning Liu
Summary: Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma in children that fails to differentiate despite expression of the myogenic determination protein MYOD. Overexpression of the TWIST2 transcription factor is frequently seen in fusion-negative RMS (FN-RMS). This study shows that knockdown of TWIST2 allows FN-RMS cells to undergo terminal myogenesis and reduces tumor growth. Mechanistically, TWIST2 controls H3K27 acetylation at distal enhancers by interacting with chromatin remodelers to regulate target genes involved in growth and myogenesis. Targeting TWIST2-regulated pathways may provide a potential treatment strategy for FN-RMS.
Article
Biochemistry & Molecular Biology
Yanpeng Li, Zhilei Li, Kutty Selva Nandakumar, Rikard Holmdahl
Summary: A recent study found that a single nucleotide variant (NCF1(R90H)) on the NCF1 gene was associated with low production of reactive oxygen species (ROS) and causative for several autoimmune diseases. The study induced psoriasis in the skin and psoriatic arthritis using mannan and evaluated the effects. It was found that the NCF1(90H) variant promoted psoriasis and psoriatic arthritis by hyperactivating macrophages, expanding keratinocytes, and increasing numbers of γδT17 cells.
Article
Immunology
Miho Shinzawa, E. Ashley Moseman, Selamawit Gossa, Yasuko Mano, Abhisek Bhattacharya, Terry Guinter, Amala Alag, Xiongfong Chen, Maggie Cam, Dorian B. McGavern, Batu Erman, Alfred Singer
Summary: The study found that the fate of T cell lineages is determined by coreceptor proteins encoded by Cd4 and Cd8 gene loci, rather than the strength of the coreceptor signal. Additionally, the researchers suggest that evolution selected specific coreceptor proteins to prevent the generation of functionally reversed T cells.
Article
Immunology
Shuo Kong, Tao-xiang Chen, Xiang-lei Jia, Xue-lei Cheng, Meng-liu Zeng, Jing-yi Liang, Xiao-hua He, Jun Yin, Song Han, Wan-hong Liu, Yuan-teng Fan, Ting Zhou, Yu-min Liu, Bi-wen Peng
Summary: NFIA upregulation in the hippocampal region is astrocyte-specific and primarily promotes detrimental actions of reactive astrocyte. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure.
JOURNAL OF NEUROINFLAMMATION
(2023)
Review
Biochemistry & Molecular Biology
Xuan Zhang, Bei-di Chen, Li-dan Zhao, Hao Li
TRENDS IN MOLECULAR MEDICINE
(2020)
Article
Immunology
Huixian Hong, Min Gao, Qi Wu, Philomena Yang, Shanrun Liu, Hao Li, Peter D. Burrows, Daniel Cua, Jake Y. Chen, Hui-Chen Hsu, John D. Mountz
JOURNAL OF IMMUNOLOGY
(2020)
Article
Rheumatology
Takayuki Katsuyama, Hao Li, Suzanne M. Krishfield, Vasileios C. Kyttaris, Vaishali R. Moulton
Summary: The study reveals a previously unrecognized role of SRSF1 in restraining IFN-gamma production and Th1 differentiation through the control of RhoH. Reduced expression of SRSF1 may contribute to the pathogenesis of autoimmune-related nephritis through these molecular mechanisms.
Review
Rheumatology
Hao Li, George C. Tsokos
Summary: DNT cells, as a principal subset of mature T lymphocytes, have been closely linked with autoimmune/inflammatory conditions. They have been found in various chronic inflammatory diseases and are proposed to play a role in both pathogenic and regulatory functions. The heterogeneity and plasticity of DNT cells need to be further understood to explore potential therapeutic interventions.
CURRENT OPINION IN RHEUMATOLOGY
(2021)
Article
Medicine, General & Internal
X. Xiao, G. Da, X. Xie, X. Liu, L. Zhang, B. Zhou, H. Li, P. Li, H. Yang, H. Chen, Y. Fei, G. C. Tsokos, L. Zhao, X. Zhang
Summary: SLE patients with concomitant TB exhibited distinct clinical characteristics compared to controls, including higher frequency of involvement in hematologic, mucocutaneous, and musculoskeletal systems, prior treatment with potent glucocorticoid/immunosuppressive agents, and an increased risk of miliary TB and intracranial TB in patients with lupus before TB infection. Lymphocytopenia was associated with poorer outcomes in SLE/TB + patients.
JOURNAL OF INTERNAL MEDICINE
(2021)
Article
Rheumatology
Bei-di Chen, Xin-Miao Jia, Jia-Yue Xu, Li-Dan Zhao, Jun-Yi Ji, Bing-Xuan Wu, Yue Ma, Hao Li, Xiao-Xia Zuo, Wen-You Pan, Xiao-Han Wang, Shuang Ye, George C. Tsokos, Jun Wang, Xuan Zhang
Summary: The study revealed significant differences in microbial composition and function in the gut microbiota of SLE patients compared to healthy controls, with certain species enriched in SLE patients and reduced after treatment. The findings were consistent in mice, and some species with an oral microbiota origin were enriched in the gut of SLE patients.
ARTHRITIS & RHEUMATOLOGY
(2021)
Article
Multidisciplinary Sciences
Junwei Zeng, Rajindra P. Aryal, Kathrin Stavenhagen, Chi Luo, Renyan Liu, Xiaohui Wang, Jiaxuan Chen, Hao Li, Yasuyuki Matsumoto, Yingchun Wang, Jianmei Wang, Tongzhong Ju, Richard D. Cummings
Summary: Deficiency in Cosmc leads to disruption of B cell tolerance, resulting in the development of autoimmune pathologies characterized by elevated levels of self-reactive antibodies, enhanced basal activation, and increased frequency of spontaneous germinal center B cells.
Article
Immunology
Hao Li, Afroditi Boulougoura, Yushiro Endo, George C. Tsokos
Summary: T cell abnormalities are closely associated with the development of SLE, including numerical and functional disturbances in CD4+ and CD8+ T cells, which lead to immune dysregulation and tissue infiltration. These abnormalities are mainly due to signaling defects, metabolic alterations, and epigenetic changes. Novel strategies to correct T cell abnormalities show promise for SLE treatment.
JOURNAL OF AUTOIMMUNITY
(2022)
Article
Multidisciplinary Sciences
Ping-Min Chen, Eri Katsuyama, Abhigyan Satyam, Hao Li, Jose Rubio, Sungwook Jung, Sylvia Andrzejewski, J. David Becherer, Maria G. Tsokos, Reza Abdi, George C. Tsokos
Summary: CD38 up-regulation in CD8(+) T cells of SLE patients negatively affects T cell function by inhibiting mitochondrial fitness and mitophagy. Targeted administration of a CD38 inhibitor improves T cell function and viral clearance, suggesting CD38 as a potential therapeutic target to mitigate infection rates in people with SLE.
Correction
Urology & Nephrology
George C. Tsokos, Afroditi Boulougoura, Vivek Kasinath, Yushiro Endo, Reza Abdi, Hao Li
NATURE REVIEWS NEPHROLOGY
(2023)
Review
Urology & Nephrology
George C. Tsokos, Afroditi Boulougoura, Vivek Kasinath, Ushiro Endo, Reza Abdi, Hao Li
Summary: The immune cells and parenchymal cells in the kidney play a significant role in the induction of kidney damage. Kidney parenchymal cells provide structural immunity to the kidney through the regulation of immune-relevant processes, affecting kidney inflammation and injury. Targeted drug delivery to kidney parenchymal cells holds promise for preventing or reversing inflammation in specific forms of kidney injury and disease.
NATURE REVIEWS NEPHROLOGY
(2023)
Article
Medicine, Research & Experimental
Hao Li, Maria G. Tsokos, Rhea Bhargava, Iannis E. Adamopoulos, Hanni Menn-Josephy, Isaac E. Stillman, Philip Rosenstiel, Jarrat Jordan, George C. Tsokos
Summary: The study found that IL-23 can affect renal tubular epithelial cells by inhibiting the expression of IL-23 receptor, increasing the levels of free arginine, suppressing T cell proliferation, and inflammatory cytokine production. The results suggest that renal tubular epithelial cells play an immunosuppressive role in regulating kidney inflammation.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Allergy
Hao Li, George C. Tsokos
Summary: Inflammatory rheumatic disorders involve the immune system attacking connective tissues and internal organs. Advances in understanding the cellular and molecular mechanisms have led to targeting the IL-23/IL-17 axis therapeutically, resulting in clinical benefits. The complicated interrelationship between IL-23 and IL-17 may be uncoupled in certain disease settings.
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Esra Meidan, Hao Li, Wenliang Pan, Michihito Kono, Shuilian Yu, Vasileios C. Kyttaris, Christina Ioannidis, Noe Rodriguez Rodriguez, Jose C. Crispin, Sokratis A. Apostolidis, Pui Lee, John Manis, Amir Sharabi, Maria G. Tsokos, George C. Tsokos
Article
Medicine, Research & Experimental
Amir Sharabi, Hao Li, Isaac R. Kasper, Wenliang Pan, Esra Meidan, Maria G. Tsokos, Vaishali R. Moulton, George C. Tsokos
