Review
Immunology
Amber Papillion, Andre Ballesteros-Tato
Summary: Novel immunotherapies such as subcutaneous low-dose r-IL2 have shown potent immunosuppressive effects in autoimmune patients, particularly on Treg cells. Additionally, rIL-2 can directly inhibit other immune cells, potentially leading to a more efficient inhibition of auto-antibody production in autoimmune patients when combined with other cytokine-based therapies.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
NanNan Fu, Fang Xie, ZhongWen Sun, Qin Wang
Summary: OX40/OX40L signaling plays a crucial role in regulating Tfh cells, promoting their differentiation, survival, and helper function for B cells. However, dysregulated OX40 signaling is associated with abnormal Tfh activity that leads to autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Hui Wang, Xiaofei Li, Tetsuhiro Kajikawa, Jieun Shin, Jong-Hyung Lim, Ioannis Kourtzelis, Kosuke Nagai, Jonathan M. Korostoff, Sylvia Grossklaus, Ronald Naumann, Triantafyllos Chavakis, George Hajishengallis
Summary: The secreted protein DEL-1 plays a critical role in regulating inflammatory cell recruitment and protecting against inflammatory arthritis. DEL-1 functions both locally in the joints and systemically in lymph nodes to inhibit Tfh responses, making it a promising therapeutic target for inflammatory arthritis treatment.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Engineering, Environmental
Haixue Jia, Yuna Shang, Hongmei Cao, Yang Gao, Jinjian Liu, Lijun Yang, Cuihong Yang, Chunhua Ren, Zhongyan Wang, Jianfeng Liu
Summary: Compared with whole pathogen vaccines, subunit vaccines based on protein antigens are safer and easier to manufacture. However, subunit vaccines usually have weak immune responses due to poor uptake by antigen-presenting cells. Researchers have developed a fluorinated aromatic peptide to improve the immune response of subunit antigens, potentially inducing cellular immune responses through antigen cross-presentation.
CHEMICAL ENGINEERING JOURNAL
(2022)
Review
Immunology
Wenjing Chen, Yuxue Cao, Yuanyuan Zhong, Jing Sun, Jingcheng Dong
Summary: CD4(+) helper T cell subsets play a critical role in the pathogenesis of asthma. Different subsets of Th cells differentiate under the stimulation of different cytokines and are driven by lineage-specific transcription factors. The balance between effector Th cell response and Treg cell immunosuppression is essential for maintaining immune homeostasis and understanding the immunopathological mechanism of asthma. Recent studies have found that certain factors involved in effector Th cell response also contribute to the development and function of Treg cells. This review aims to summarize the role of these factors in Treg cell development and function to gain new insights into the immunopathological mechanism and potential therapy strategies of asthma.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Yu Jiang, Xuexiao Jin, Zhexu Chi, Yadan Bai, Kalpana Manthiram, Pamela Mudd, Kaixiang Zhu, Lie Wang, Pamela L. Schwartzberg, Yongmei Han, Xiang Gao, Linrong Lu, Qin Xu
Summary: Follicular helper T (Tfh) cells play a crucial role in promoting immune responses, but their abnormal expansion can lead to the generation of harmful autoantibodies and autoimmune diseases such as systemic lupus erythematosus (SLE). This study demonstrates that elevated levels of PP2A C alpha, a protein phosphatase, in T cells of SLE patients are associated with increased autoantibody titers and disease activity. PP2A deficiency impairs Tfh differentiation and GC response, while targeting PP2A can alleviate lupus severity in mice. These findings suggest that PP2A may be a potential therapeutic target for SLE.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Immunology
Ryan Zander, Moujtaba Y. Kasmani, Yao Chen, Paytsar Topchyan, Jian Shen, Shikan Zheng, Robert Burns, Jennifer Ingram, Can Cui, Nikhil Joshi, Joseph Craft, Allan Zajac, Weiguo Cui
Summary: This study found that CD4(+) T cells consist of three distinct subsets during chronic viral infection, and IL-21 derived from Tfh cells is critical for sustaining CD8(+) T cell responses and viral control.
Article
Gastroenterology & Hepatology
Anna-Maria Globig, Nikola Patricia Sommer, Katharina Wild, Josefine Schardey, Katharina Zoldan, Anne Kerstin Thomann, Lucas-Alexander Schulte, Rupert Schreiner, Wolfgang Reindl, Jochen Klaus, Christoph Mathis Schempp, Maike Hofmann, Robert Thimme, Tobias Boettler, Peter Hasselblatt
Summary: TFH cells play a crucial role in the pathogenesis of CD, and Ustekinumab therapy affects TFH cell differentiation, thus influencing TFH-mediated immune functions in UST-treated CD patients.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shuaifeng Yan, Viktoria Golumba-Nagy, Konstantin Kotschenreuther, Jan Thiele, Nasrin Refaian, Deng Shuya, Lydia Gloyer, Mara Dittrich-Salamon, Anja Meyer, Ludwig M. Heindl, David M. Kofler
Summary: This study reveals that membrane-bound IL-6 receptor (IL6R) expression is upregulated on Th17 cells in autoimmune arthritis, and is inversely correlated with IL-6 serum levels. Additionally, the migratory function of Treg cells is impaired in autoimmune arthritis due to decreased phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Blockade of IL-6R restores VASP phosphorylation and improves Treg cell migration.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biology
Lin Jin, Ziwei Zhang, Pin Pan, Yuchen Zhao, Mengqi Zhou, Lianghu Liu, Yuanfang Zhai, Han Wang, Li Xu, Dan Mei, Han Zhang, Yining Yang, Jinghan Hua, Xianzheng Zhang, Lingling Zhang
Summary: The study found that ethanol consumption can reduce the severity of autoimmune arthritis by affecting the levels of the gut microbiota metabolite acetate. Acetate plays a role by regulating neutrophil activity and inhibiting the formation of neutrophil extracellular traps.
COMMUNICATIONS BIOLOGY
(2023)
Article
Immunology
Jianqiao Hong, Zihao Qu, Xiaoxiao Ji, Congsun Li, Geng Zhang, Ciliang Jin, Jie Wang, Yongxing Zhang, Yue Shen, Jiahong Meng, Chenhe Zhou, Chaohua Fang, Wei Wang, Shigui Yan
Summary: The study revealed that the overactive IL6 signal pathway contributes to the development of autoimmune arthritis, especially in rheumatoid arthritis and ankylosing spondylitis. Furthermore, a sexual difference was observed in the susceptibility to autoimmune arthritis associated with IL6.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Alexander Blagov, Andrey Grechko, Nikita G. Nikiforov, Alexander D. Zhuravlev, Nikolay K. Sadykhov, Alexander N. Orekhov
Summary: This article discusses the connection between metabolism and inflammation in rheumatoid arthritis, exploring the changes in metabolic processes and their immunomodulatory effects, as well as the metabolic features of synovial membrane cells during inflammation and potential targets for the therapy of rheumatoid arthritis.
Article
Immunology
Paola V. Ferrero, Luisina I. Onofrio, Cristina del Valle Acosta, Estefania R. Zacca, Nicolas E. Ponce, Eduardo Mussano, Laura B. Onetti, Ignacio I. Cadile, Alicia B. Costantino, Marina L. Werner, Luciana A. Mas, Teresita Alvarellos, Carolina L. Montes, Eva V. Acosta Rodriguez, Adriana Gruppi
Summary: The subsets of Tfh and Tfr cells in rheumatoid arthritis (RA) show altered dynamics after treatment and are associated with HLA class-II variants and disease activity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Jeong Hyun Lee, Joyce K. Hu, Erik Georgeson, Catherine Nakao, Bettina Groschel, Thamotharampillai Dileepan, Marc K. Jenkins, Gregory Seumois, Pandurangan Vijayanand, William R. Schief, Shane Crotty
Summary: The quantity of CD4 T cell help has been found to influence recruitment and competition of broadly neutralizing antibody precursor B cells in response to Env trimer immunization. This finding is crucial for designing vaccines against diseases of high interest.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Immunology
Fuping Shen, Yuhuan Shen, Yuni Xu, Jiwei Zhao, Zhao Zhao, Jinlin Liu, Yumei Ge
Summary: This study investigates the changes in T follicular helper T (Tfh) cell balance among patients with secondary syphilis and latent syphilis. The results show that the percentage of total Tfh cells is significantly higher in secondary syphilis patients compared to healthy controls, while only ICOS+ Tfh and effector memory Tfh cells showed significant increases in secondary syphilis patients and decreases in latent syphilis patients. PD-1+ Tfh cells, central memory Tfh cells, and Tfh2 cells also showed significant increases in latent syphilis patients. Meanwhile, naive Tfh cells and Tfh1 cells exhibited significant decreases in secondary syphilis patients when compared to the healthy controls. However, no significant change was found in resting Tfh and effector Tfh in any of the groups.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Nanoscience & Nanotechnology
Lidia Almenara-Fuentes, Silvia Rodriguez-Fernandez, Estela Rosell-Mases, Katerina Kachler, Axel You, Miriam Salvado, Darja Andreev, Ulrike Steffen, Holger Bang, Aline Bozec, Georg Schett, Rozen Le Panse, Joan Verdaguer, Marti Dalmases, Silvia Rodriguez-Vidal, Bruna Barneda-Zahonero, Marta Vives-Pi
Summary: This study demonstrates the therapeutic potential of using phosphatidylserine (PS)-liposomes encapsulating autoantigens to treat various autoimmune diseases. These specific PS-liposomes have shown preventive and therapeutic efficacy in restoring self-tolerance and immunoregulation.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2023)
Article
Cell Biology
Julia Elrod, Antonia Kiwit, Moritz Lenz, Holger Rohde, Daniela Boernigen, Malik Alawi, Christoph Mohr, Laia Pagerols Raluy, Magdalena Trochimiuk, Jasmin Knopf, Konrad Reinshagen, Martin Herrmann, Michael Boettcher
Summary: This study evaluated the septic volvulus ischemia-reperfusion model and compared it to two established models in mice sepsis. The results showed that midgut volvulus for 15 minutes caused a comparable mortality rate as the other two models, and at 48 hours, there was a decrease in circulating free DNA levels and an increase in bacterial translocation to the spleen/liver and lungs. In addition, DNases were increased in this model compared to the established models. Proteomic analysis revealed an upregulation of several markers of inflammation and tissue damage at 48 hours. Overall, this study demonstrates that midgut volvulus is a stable and physiological model for studying sepsis.
Article
Immunology
Pascal Irrgang, Juliane Gerling, Katharina Kocher, Dennis Lapuente, Philipp Steininger, Katharina Habenicht, Monika Wytopil, Stephanie Beileke, Simon Schaefer, Jahn Zhong, George Ssebyatika, Thomas Krey, Valeria Falcone, Christine Schuelein, Antonia Sophia Peter, Krystelle Nganou-Makamdop, Hartmut Hengel, Juergen Held, Christian Bogdan, Klaus Ueberla, Kilian Schober, Thomas H. Winkler, Matthias Tenbusch
Summary: RNA vaccines are effective in preventing SARS-CoV-2 infection, and high levels of neutralizing antibodies are crucial for vaccine-induced immunity. After the second mRNA vaccination, SARS-CoV-2-specific antibodies were increasingly composed of noninflammatory IgG4, which was further boosted by a third vaccination or breakthrough infections. This induction of IgG4 antibodies was not observed with adenoviral vectors. These findings have implications for the choice and timing of mRNA vaccine regimens, including booster shots.
SCIENCE IMMUNOLOGY
(2023)
Article
Rheumatology
Maria Sokolova, Fabian Hartmann, Daniela Sieghart, Holger Bang, Guenter Steiner, Arnd Kleyer, Georg Schett, Ulrike Steffen
Summary: The study aimed to investigate the events triggering disease outbreak in individuals at-risk for rheumatoid arthritis (RA at-risk) and the role of different isotypes of anticitrullinated protein antibody (ACPA) in this process. Serum levels of IgA1 and IgA2 ACPA were measured, and it was found that approximately two-thirds of at-risk individuals tested positive for IgA1 and IgA2 ACPA, with IgA1 ACPA being associated with the progression to RA. The decline in serum IgA1 ACPA levels before the onset of RA may indicate starting barrier leakiness prior to disease outbreak.
Review
Biochemistry & Molecular Biology
Jeeshan Singh, Michael Boettcher, Maximilian Doelling, Annika Heuer, Bettina Hohberger, Moritz Leppkes, Elisabeth Naschberger, Mirco Schapher, Christine Schauer, Janina Schoen, Michael Stuerzl, Ljubomir Vitkov, Han Wang, Leticija Zlatar, Georg A. Schett, David S. Pisetsky, Ming-Lin Liu, Martin Herrmann, Jasmin Knopf
Summary: Extracellular chromatin, particularly in the form of NETs, plays a crucial role in the progression of various diseases. It functions as a driver of the interferon system, autoantigen, and scaffold for innate immune system proteins. Insufficient clearance of extruded chromatin can contribute to immune-inflammatory and occlusive disorders. This article discusses the cellular events involved in extracellular chromatin release and NET formation, the negative consequences of dysregulated NET formation, and the imbalance between NET formation and clearance. It also explores the role of NET formation in various diseases and injuries, highlighting the importance of targeting chromatin decondensation pathways and promoting extracellular chromatin clearance for effective therapies.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Biochemistry & Molecular Biology
Han Wang, Antonia Margarethe Stehr, Jeeshan Singh, Leticija Zlatar, Arndt Hartmann, Katja Evert, Elisabeth Naschberger, Saskia von Stillfried, Peter Boor, Luis E. E. Munoz, Jasmin Knopf, Michael Stuerzl, Martin Herrmann
Summary: During inflammatory responses, neutrophils utilize various defense mechanisms, such as phagocytosis, degranulation, recruitment of immune cells, secretion of anti-microbials, and release of neutrophil extracellular traps (NETs). Detection of NETs in tissue sections can be challenging due to the high fluorescence signals emitted from condensed nuclear DNA. However, using anti-DNA-IgM antibodies can effectively detect the extended DNA patches of NETs, providing a new perspective for studying neutrophil-associated immune reactions in diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Ljubomir Vitkov, Jeeshan Singh, Christine Schauer, Bernd Minnich, Jelena Krunic, Hannah Oberthaler, Sonja Gamsjaeger, Martin Herrmann, Jasmin Knopf, Matthias Hannig
Summary: The break of the epithelial barrier of gingiva has been a neglected topic despite its significant role in periodontal pathology and transitory bacteraemia. Mechanically induced bacterial translocation in gingiva has been disregarded despite the knowledge of mechanical force effects on tight junctions in other epithelial tissues. In this review, the bacterial, immune, and mechanical factors responsible for the increased permeability and break of the epithelial barrier of inflamed gingiva are discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Xue Cao, Yanhong Li, Yubin Luo, Tianshu Chu, Hang Yang, Ji Wen, Yi Liu, Yi Zhao, Martin Herrmann
Summary: The formation of neutrophil extracellular traps (NETs) plays a role in infection-related and sterile inflammation. Monosodium urate (MSU) crystals are involved in various diseases as damage-associated molecular patterns (DAMPs). The study demonstrates that the ROS-sensing channel TRPM2 is necessary for MSU crystal-induced NET formation and TRPM2 knockout leads to reduced inflammation. This indicates that TRPM2 could be a potential target for therapeutic intervention.
JOURNAL OF INFLAMMATION-LONDON
(2023)
Article
Plant Sciences
Christian E. Lamm, Ismail Y. Rabbi, David Barbosa Medeiros, Laise Rosado-Souza, Benjamin Pommerrenig, Ismail Dahmani, David Ruescher, Joerg Hofmann, Anna M. van Doorn, Armin Schlereth, H. Ekkehard Neuhaus, Alisdair R. Fernie, Uwe Sonnewald, Wolfgang Zierer
Summary: Cassava's storage roots are a vital source of nutritional carbohydrates globally, especially for smallholder farmers in sub-Saharan Africa. Through analyzing the metabolic and proteomic profiles of different cassava genotypes, we identified key metabolic patterns associated with high dry matter accumulation in storage roots. These findings contribute to our understanding of cassava's metabolism and can be used for targeted genetic improvement.
Article
Immunology
Julia Elrod, Moritz Lenz, Antonia Kiwit, Lina Armbrust, Lavinia Schoenfeld, Konrad Reinshagen, Laia Pagerols Raluy, Christoph Mohr, Ceren Saygi, Malik Alawi, Holger Rohde, Martin Herrmann, Michael Boettcher
Summary: Through optimizing a murine scald model, this study investigated the immune responses to heat induced injury. The study identified the roles of neutrophil extracellular traps (NETs) and DNases in the therapy of burns. It also evaluated the effects of different exposure times on extracellular matrix.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Michael Frech, Heike Danzer, Pooja Uchil, Vugar Azizov, Eva Schmid, Fabian Schalter, Kerstin Durholz, Daniele Mauro, Simon Rauber, Luis Munoz, Leila Taher, Francesco Ciccia, Kilian Schober, Magali Irla, Kerstin Sarter, Georg Schett, Mario M. Zaiss
Summary: Butyrophilin 2a2 (Btn2a2), predominantly expressed by thymic epithelial cells (TEC), inhibits conventional T cell activation and affects thymic T cell maturation and central tolerance mechanisms. Btn2a2-/- mice develop spontaneous autoimmunity resembling human primary Sjögren's Syndrome (pSS), including the formation of tertiary lymphoid structures (TLS) in target organs.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Cell Biology
Leticija Zlatar, Thomas Timm, Gunter Lochnit, Rostyslav Bilyy, Tobias Baeuerle, Marco Munoz-Becerra, Georg Schett, Jasmin Knopf, Jens Heichel, Mohammad Javed Ali, Mirco Schapher, Friedrich Paulsen, Martin Herrmann
Summary: Mucopeptide concretions, also known as dacryoliths, are macroscopic stones that commonly block the lacrimal sac. The mechanisms behind their formation are unclear, but various immune cells, including neutrophils, have been confirmed to be involved. This study investigates the role of neutrophils and neutrophil extracellular traps (NETs) in dacryolithiasis using multiple analysis methods, and proposes a mechanism for the formation and growth of mucopeptide concretions involving neutrophils and NETs.
Review
Immunology
Dennis Lapuente, Thomas H. Winkler, Matthias Tenbusch
Summary: This review summarizes the key findings of the last 2.5 years regarding B-cell immunity induced by SARS-CoV-2 infection and vaccines, which are of significant value for future vaccination approaches in endemic and pandemic settings.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sarah Schlick, Marianna Lucio, Gerd Wallukat, Alexander Bartsch, Adam Skornia, Jakob Hoffmanns, Charlotte Szewczykowski, Thora Schroeder, Franziska Raith, Lennart Rogge, Felix Heltmann, Michael Moritz, Lorenz Beitlich, Julia Schottenhamml, Martin Herrmann, Thomas Harrer, Marion Ganslmayer, Friedrich E. Kruse, Robert Laemmer, Christian Mardin, Bettina Hohberger
Summary: This study investigated the potential association between self-reported chronic fatigue and retinal microcirculation in patients with Post-COVID-19 syndrome (PCS). The results suggest that retinal microcirculation may serve as an objective biomarker for chronic fatigue in PCS patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)