Article
Immunology
Masashi Morita, Masayuki Mizui, Satoshi Masuyama, George C. Tsokos, Yoshitaka Isaka
Summary: The study compares the efficacy and mechanisms of action of conventional anti-CD3 antibodies and non-mitogenic anti-CD3 antibodies. It demonstrates that non-mitogenic anti-CD3 antibodies can effectively suppress the development of lupus by reducing surface TCR.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Yazhong Cui, Yang Miao, Longzhi Cao, Lifang Guo, Yue Cui, Chuanzhe Yan, Zhi Zeng, Mo Xu, Ting Han
Summary: The loss of melanocortin-1 receptor (MC1R) in melanoma cells is associated with enhanced T cell infiltration and anti-tumor immune responses.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Yiying Yang, Muyuan Li, Yaxi Zhu, Ke Liu, Meidong Liu, Yanjuan Liu, Ganqian Zhu, Hui Luo, Xiaoxia Zuo, Huali Zhang, Muyao Guo
Summary: The aim of this study was to elucidate the role of enhancer of zeste homolog 2 (EZH2) in the breakdown of B cell immune tolerance and production of autoantibodies in systemic lupus erythematosus (SLE), and to explore the therapeutic effects of EZH2 inhibition on lupus. EZH2 expression was elevated in diverse B-cell subsets in both SLE patients and pristane-induced lupus mice. The EZH2 inhibitor attenuated lupus-like symptoms and dampened autoantibody production in pristane-induced lupus mice.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Immunology
Jeremy S. Tilstra, Minjung Kim, Rachael A. Gordon, Claire Leibler, Haylee A. Cosgrove, Sheldon Bastacky, Kevin M. Nickerson, Mark J. Shlomchik
Summary: Studies have shown that MyD88 in B cells plays a crucial role in the onset and progression of lupus in mice, and its deficiency can improve disease symptoms and reduce autoantibody production. Therefore, targeting MyD88 or its upstream activators may be an effective option for treating lupus.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Immunology
James J. Pestka, Peyman Akbari, Kathryn A. Wierenga, Melissa A. Bates, Kristen. N. Gilley, James G. Wagner, Ryan P. Lewandowski, Lichchavi D. Rajasinghe, Preeti S. Chauhan, Adam L. Lock, Quan-Zhen Li, Jack R. Harkema
Summary: Dietary intervention with DHA found in fish oil was found to suppress or delay the progression of lupus triggered by environmental toxicant in a mouse model.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Azusa Kobayashi, Ayaka Ito, Ibuki Shirakawa, Atsushi Tamura, Susumu Tomono, Hideo Shindou, Per Niklas Hedde, Miyako Tanaka, Naotake Tsuboi, Takuji Ishimoto, Sachiko Akashi-Takamura, Shoichi Maruyama, Takayoshi Suganami
Summary: Accumulating evidence suggests that cholesterol accumulation in leukocytes is causally associated with autoimmune diseases, but the mechanism by which fatty acid composition affects autoimmune responses remains unclear. Dietary supplementation of EPA has been found to ameliorate lupus manifestations by remodeling B cell membranes, preventing differentiation into autoantibody-producing plasma cells. These results highlight a potential therapeutic benefit of EPA supplementation for lupus.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Kelsey Voss, Allison E. Sewell, Evan S. Krystofiak, Katherine N. Gibson-Corley, Arissa C. Young, Jacob H. Basham, Ayaka Sugiura, Emily N. Arner, William N. Beavers, Dillon E. Kunkle, Megan E. Dickson, Gabriel A. Needle, Eric P. Skaar, W. Kimryn Rathmell, Michelle J. Ormseth, Amy S. Major, Jeffrey C. Rathmell
Summary: T cells in systemic lupus erythematosus (SLE) exhibit metabolic abnormalities, with excess iron playing a potential role in SLE pathogenesis. The transferrin receptor (CD71) is critical for T(H)1 cells and inhibitory for induced regulatory T cells (iT(regs)). Increased CD71 expression and iron uptake were observed in activated T cells, particularly in SLE-prone T cells. Blocking CD71 reduced intracellular iron, mTORC1 signaling, and the production of T(H)1 and T(H)17 cells, while enhancing iT(regs) and IL-10 secretion. In vivo treatment targeting CD71 reduced kidney pathology in SLE-prone mice. CD71 expression on T(H)17 cells correlated with disease severity in SLE patients. Thus, T cell iron uptake via CD71 contributes to T cell dysfunction and can be targeted to limit SLE-associated pathology.
SCIENCE IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Haylee A. Cosgrove, Sebastien Gingras, Minjung Kim, Sheldon Bastacky, Jeremy S. Tilstra, Mark J. Shlomchik
Summary: The regulatory role of Toll-like receptor 7 (TLR7) in the pathogenesis of lupus and its potential therapeutic strategy have been studied. The study found that TLR7 deficiency in B cells greatly improved the disease progression in TLR9-deficient mice with accelerated systemic lupus erythematosus, suggesting the importance of B cell-directed TLR7 regulation in lupus.
Article
Immunology
Miles B. Horton, HoChan Cheon, Ken R. Duffy, Daniel Brown, Shalin H. Naik, Carolina Alvarado, Joanna R. Groom, Susanne Heinzel, Philip D. Hodgkin
Summary: This study reveals that B lymphocytes generate plasma cells with diverse antibody isotypes, and their fate is regulated by discrete mechanisms. Founder cells have a major influence on clonal plasma-cell fate, while class switch recombination (CSR) shows variation within clones. The CSR patterns are determined by the independent all-or-none expression of activation-induced cytidine deaminase and IgH germline transcription.
Article
Immunology
Lauren K. Heine, Abby D. Benninghoff, Elizabeth A. Ross, Lichchavi D. Rajasinghe, James G. Wagner, Ryan P. Lewandowski, Alexa L. Richardson, Quan-Zhen Li, John P. Buchweitz, Justin Zyskowski, Ashleigh N. Tindle, Anna E. Skedel, Nicholas J. Chargo, Laura R. McCabe, Jack R. Harkema, James J. Pestka
Summary: The study revealed that moderate doses of prednisone can reduce important pathological endpoints of cSiO(2)-induced autoimmune disease in lupus-prone mice, but come with unwanted hormonal toxicity, and none of the three doses extended survival time.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Emma J. Keller, Neeva B. Patel, Madeline Patt, Jane K. Nguyen, Trine N. Jorgensen
Summary: Research indicates that in SLE patients, IFN alpha beta signaling in B cells leads to splenomegaly, increased populations of activated B cells, germinal center B cells, memory B cells, and plasma blasts/cells, while not affecting the development of glomerulonephritis and immune-complex deposition.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Gaetano Calcagno, Jeremy Jeandel, Jean-Pol Frippiat, Sandra Kaminski
Summary: Different forms of stress in spaceflights impact the immune system and specifically dendritic cells. Hypergravity induces a less mature phenotype in dendritic cells, while simulated microgravity reduces their activation and pro-inflammatory cytokine production. Microgravity also impairs dendritic cells' ability to induce a proper immune response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Kongyang Ma, Wenhan Du, Fan Xiao, Man Han, Enyu Huang, Na Peng, Yuan Tang, Chong Deng, Lixiong Liu, Yulan Chen, Jingjing Li, Shiwen Yuan, Qin Huang, Xiaoping Hong, Dajun Hu, Xiaoyan Cai, Quan Jiang, Dongzhou Liu, Liwei Lu
Summary: The study demonstrated the crucial role of IL-17 in enhancing plasma cell survival and promoting autoantibody production in the pathogenesis of SLE. This discovery may offer new therapeutic strategies for the treatment of SLE.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Samantha A. Chalmers, Rajalakshmy Ayilam Ramachandran, Sayra J. Garcia, Evan Der, Leal Herlitz, Jeanette Ampudia, Dalena Chu, Nicole Jordan, Ting Zhang, Ioannis Parodis, Iva Gunnarsson, Huihua Ding, Nan Shen, Michelle Petri, Chi Chiu Mok, Ramesh Saxena, Krishna R. Polu, Stephen Connelly, Cherie T. Ng, Chandra Mohan, Chaim Putterman
Summary: CD6/ALCAM pathway plays a crucial role in the pathogenesis of lupus nephritis (LN) and systemic lupus erythematosus (SLE), contributing to T cell activation and trafficking. Furthermore, uALCAM is a potential biomarker for active renal involvement in SLE, independent of ethnicity.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Immunology
Wangbin Ning, Da Cheng, Philip H. Howe, Chuanxiu Bian, Diane L. Kamen, Zhenwu Luo, Xiaoyu Fu, Elizabeth Ogunrinde, Liuqing Yang, Xu Wang, Quan-Zhen Li, Jim Oates, Weiru Zhang, David White, Zhuang Wan, Gary S. Gilkeson, Wei Jiang
Summary: The interaction between the microbiome and the immune response plays a crucial role in the development of normal immunity and autoimmunity. This study found that peptidoglycan (PGN) from different bacteria can have different effects on the production of autoantibodies: PGN from Bacillus subtilis drives the production of natural nonpathogenic autoantibodies, while PGN from Staphylococcus aureus induces the production of pathogenic autoantibodies.
JOURNAL OF AUTOIMMUNITY
(2022)
Article
Immunology
Jingwei Wang, Tianbao Li, Hong Zan, Carlos E. Rivera, Hui Yan, Zhenming Xu
Summary: The study showed that LUBAC controls cFLIP expression, inhibits the effects of caspase 8 and IL-21-activated caspase 9, thereby suppressing apoptosis of CD40 and IL-21-activated B cells, promoting GC B cell survival.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Zengzi Zhou, Qi Tian, Luying Wang, Min Xue, Dabao Xu, Guangming Zhong
Summary: Genital Chlamydia can spread to the gastrointestinal tract without the spleen, possibly through a spleen-to-stomach and liver-to-intestine pathways.
INFECTION AND IMMUNITY
(2021)
Article
Immunology
Qi Tian, Zengzi Zhou, Luying Wang, Xin Sun, Bernard Arulanandam, Dabao Xu, Min Xue, Guangming Zhong
Summary: The study demonstrates that CD8(+) T cells induced by gastrointestinal Chlamydia are both necessary and sufficient for promoting hydrosalpinx in the genital tract.
INFECTION AND IMMUNITY
(2021)
Article
Immunology
Zengzi Zhou, Qi Tian, Luying Wang, Xin Sun, Nu Zhang, Min Xue, Dabao Xu, Guangming Zhong
Summary: This study validated the critical role of CD8(+) T cells in the induction of hydrosalpinx caused by Chlamydia trachomatis. CD8(+) T cells from wild type C57BL/6J mice were able to promote hydrosalpinx in OT1 mice through transfer. However, this promotion needed to be initiated within 2 weeks after infection, and once initiated, CD8(+) T cells could continue to promote hydrosalpinx for more than 3 weeks.
INFECTION AND IMMUNITY
(2022)
Article
Immunology
Zengzi Zhou, Qi Tian, Luying Wang, Guangming Zhong
Summary: Despite efforts, there is still no licensed vaccine against Chlamydia trachomatis. Mouse models have helped study the pathogenic mechanisms and vaccine candidates, with mutants showing reduced pathogenicity in inducing disease. Further research is needed to develop safe and effective vaccines.
INFECTION AND IMMUNITY
(2022)
Article
Immunology
Xin Su, Hong Xu, Maegan French, Yujie Zhao, Lingli Tang, Xiao-dong Li, Jianlin Chen, Guangming Zhong
Summary: Sexually transmitted Chlamydia trachomatis can ascend to the upper genital tract but is susceptible to innate immunity in the lower genital tract of mice. The cGAS-STING signaling pathway plays an essential role in the innate immunity against C. trachomatis infection in the mouse genital tract.
INFECTION AND IMMUNITY
(2022)
Article
Multidisciplinary Sciences
Yijang Xu, Hang Zhou, Ginell Post, Hong Zan, Paolo Casali
Summary: The study demonstrates that Rad52 mediates IgD CSR through a microhomology-based DNA repair pathway, leading to the expression of IgD in B cells.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Mengxing Li, Suryavathi Viswanadhapalli, Bindu Santhamma, Uday P. Pratap, Yiliao Luo, Junhao Liu, Kristin A. Altwegg, Weiwei Tang, Zexuan Liu, Xiaonan Li, Behnam Ebrahimi, Hui Yan, Yi Zou, Swapna Konda, Gangadhara R. Sareddy, Zhenming Xu, Yidong Chen, Manjeet K. Rao, Andrew J. Brenner, Virginia G. Kaklamani, Rajeshwar R. Tekmal, Gulzar Ahmed, Ganesh Raj, Klaus J. Nickisch, Hareesh B. Nair, Ratna K. Vadlamudi
Summary: The study demonstrated that LIFR inhibitor EC359 could enhance the therapeutic efficacy of HDACi against TNBC, with RNA-seq studies showing that the combination therapy attenuated oncogenic/survival signaling pathways activated by HDACi. Importantly, the combination therapy showed potent inhibition of TNBC growth in vivo.
COMMUNICATIONS BIOLOGY
(2021)
Article
Medicine, General & Internal
Decai Zhang, Shaojun Liu, Zhaoqi Li, Rui Wang
Summary: This study evaluated the latest epidemiologic patterns and trends for GERD using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The results showed that the burden of GERD is continuing to worsen, with a higher prevalence among females compared to males. Higher socio-demographic index (SDI) was associated with lower incidence and years of life lived with disability (YLDs) for GERD in 2019.
ANNALS OF MEDICINE
(2022)
Article
Immunology
Yujie Zhao, Zhi Huo, Zengzi Zhou, Christian Cervantes, Jianlin Chen, Zhenming Xu, Guangming Zhong
Summary: In this study, it was found that IL-27 may promote chlamydial infection in the female mouse genital tract and increase chlamydial burden by suppressing IFN-gamma-mediated immunity. Knocking out IL-27R from T cells alone significantly shortened the infectious shedding courses of Chlamydia in the mouse genital tract. These findings suggest that attenuating IL-27 signaling in T cells may be used to enhance genital tract immunity against chlamydial infection.
INFECTION AND IMMUNITY
(2022)
Article
Immunology
Rongze He, Caroline Andrea Torres, Yihui Wang, Cheng He, Guangming Zhong
Summary: We found that Chlamydia trachomatis is inhibited during early infection in the female mouse genital tract and that the innate immunity against C. trachomatis is compromised without cGAS-STING signaling. We evaluated the impact of type-I interferon signaling on C. trachomatis infection in the female genital tract. Our results showed that mice lacking the type-I interferon receptor (IFN alpha R1) had significantly higher levels of live chlamydial organisms on days 3 and 5, demonstrating the protective role of type-I interferon signaling in preventing C. trachomatis infection in the mouse genital tract.
INFECTION AND IMMUNITY
(2023)
Article
Medicine, General & Internal
Rui Wang, Zhaoqi Li, Shaojun Liu, Decai Zhang
Summary: The global burden of inflammatory bowel disease (IBD) is increasing, with higher numbers of cases, deaths, and DALYs among females than males. Understanding the changing epidemiological trends and disease burden of IBD is important for policy makers to develop effective management strategies.
Article
Multidisciplinary Sciences
Carlos E. Rivera, Yulai Zhou, Daniel P. Chupp, Hui Yan, Amanda D. Fisher, Raphael Simon, Hong Zan, Zhenming Xu, Paolo Casali
Summary: Maturation of antibody responses involves B cell Toll-like receptor (TLR) coengagement with B cell receptor (BCR), leading to various processes including somatic hypermutation (SHM), class-switch DNA recombination (CSR), plasma cell differentiation, and memory B cell generation. TLR-BCR coengagement requires linkage of TLR and BCR ligands, and it can induce mature antibody responses and protective antibodies against microbial pathogens, such as Escherichia coli and Salmonella Typhi-murium, without T cell help.
Article
Public, Environmental & Occupational Health
Rui Wang, Zhaoqi Li, Shaojun Liu, Decai Zhang
Summary: According to the global burden of disease study, digestive diseases pose a significant burden worldwide and vary by age, sex, sociodemographic index, and geographical region. Cirrhosis and other chronic liver diseases are the leading contributors to the burden of digestive diseases globally. The age-standardized rate of digestive disease DALYs has decreased from 1990 to 2019, and alcohol use is the largest contributor to the global burden of digestive diseases.
FRONTIERS IN PUBLIC HEALTH
(2023)
Article
Immunology
Chunxue Lu, Jie Wang, Guangming Zhong
Summary: Evaluation of different immunization regimens showed that viable chlamydial organisms were superior in preventing both genital infection and pathology. However, no suitable subunit vaccine candidate was identified.
INFECTION AND IMMUNITY
(2023)