Article
Gastroenterology & Hepatology
Tiong Y. Lim, Elena Perpinan, Maria-Carlota Londono, Rosa Miquel, Paula Ruiz, Ada S. Kurt, Elisavet Kodela, Amy R. Cross, Claudia Berlin, Joanna Hester, Fadi Issa, Abdel Douiri, Felix H. Volmer, Richard Taubert, Evangelia Williams, Anthony J. Demetris, Andrew Lesniak, Gilbert Bensimon, Juan Jose Lozano, Marc Martinez-Llordella, Tim Tree, Alberto Sanchez-Fueyo
Summary: This study investigated the role of low-dose IL-2 (LDIL-2) in maintaining liver allograft tolerance. The results showed that LDIL-2 expanded circulating regulatory T cells (Tregs) but failed to effectively suppress antigen-specific immune responses and promote the accumulation of intrahepatic Tregs. Furthermore, LDIL-2 induced a liver transcriptional response even before immunosuppression weaning. The study was terminated after the first 6 participants failed to reach the primary endpoint, requiring reinstitution of immunosuppression.
JOURNAL OF HEPATOLOGY
(2023)
Article
Immunology
Danielle M. Santarelli, Fabien B. Vincent, Ina Rudloff, Claudia A. Nold-Petry, Marcel F. Nold, Marc A. Russo
Summary: The study aimed to establish the first reference range of circulating IL-37 levels in healthy adult humans by analyzing 19 studies. The preliminary findings indicate that IL-37 levels were higher in the Chinese population and further large, prospective, multi-ethnic studies are needed to determine a reliable reference range for clinical application. Additionally, factors such as demographics, sample matrix, collection, processing, and storage methods that could affect IL-37 detection levels should be thoroughly investigated.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Yutaka Matsumura, Rei Watanabe, Manabu Fujimoto
Summary: B cells, including regulatory B cells (Bregs), regulate inflammation through an inhibitory mechanism mediated by interleukin 10 (IL-10). Bregs have been reported in various disease models and play a role in autoimmune diseases, infectious diseases, cancer, and organ-transplant rejection. In addition to IL-10, other cytokines and membrane-binding molecules are also involved in the suppressive functions of Bregs. The identification and classification of Breg fractions remains challenging due to the variations in their activity and differentiation stages in different disease models.
INTERNATIONAL IMMUNOLOGY
(2023)
Article
Immunology
Hiroshi Kato, Andras Perl
Summary: IL-2 treatment can expand Treg cell population while also potentially increasing pro-inflammatory cells, showing varying effects on SLE patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Bo Zhang, Jiaqi Sun, Yeshuang Yuan, Dezhong Ji, Yeting Sun, Yudong Liu, Shengjie Li, Xingxing Zhu, Xunyao Wu, Jin Hu, Qiu Xie, Ling Wu, Lulu Liu, Boyang Cheng, Yuanjie Zhang, Lingjuan Jiang, Lidan Zhao, Fei Yu, Wei Song, Min Wang, Yue Xu, Shiliang Ma, Yunyun Fei, Lihe Zhang, Demin Zhou, Xuan Zhang
Summary: In this study, a strategy was developed to selectively activate regulatory T cells (Tregs) using IL-2 variants that covalently bind to IL-2R alpha. The IL-2 variants, containing a bioreactive artificial amino acid, fluorosulfate-L-tyrosine (FSY), showed enhanced therapeutic efficacy in murine models of lupus and graft-versus-host disease (GvHD). Furthermore, N-terminal PEGylation of the IL-2 variants improved their circulatory retention and sustained effects. This proximity-enabled covalent binding strategy has the potential to accelerate the development of immunomodulatory therapies.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Rafael Saup, Nidhi Nair, Jingyi Shen, Anja Schmaus, Wilko Thiele, Boyan K. Garvalov, Jonathan P. Sleeman
Summary: The role of circulating osteopontin (cOPN) in melanoma progression was studied. It was found that increased cOPN promotes primary tumor growth but does not significantly affect spontaneous metastasis of melanoma cells to lymph nodes or lungs.
Article
Immunology
Pooja Mehta, Victoire Gouirand, Devi P. Boda, Jingxian Zhang, Sofia Gearty, Bahar Zirak, Margaret M. Lowe, Sean Clancy, Ian Boothby, Kelly M. Mahuron, Adam Fries, Matthew F. Krummel, Parminder Mankoo, Hsin-Wen Chang, Jared Liu, Joshua M. Moreau, Tiffany C. Scharschmidt, Adil Daud, Esther Kim, Isaac M. Neuhaus, Hobart W. Harris, Wilson Liao, Michael D. Rosenblum
Summary: The study identifies LAYN (layilin) as preferentially expressed on a subset of activated Tregs in human skin, with a role in facilitating Treg adhesion and limiting their suppressive capacity. This mechanism may influence Treg motility and immune regulation in nonlymphoid tissues, potentially guiding therapeutic strategies for immune modulation.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Cell Biology
Daniel S. Shin, Sneha Ratnapriya, Creel Ng Cashin, Lucy F. Kuhn, Rod A. Rahimi, Robert M. Anthony, James J. Moon
Summary: Self-antigen-specific T cells are regulated through tolerance mechanisms, but tissue injury can disrupt this regulation and trigger autoimmunity. Using mouse models of lung injury, we found that acute injury leads to the expansion of CD4+ regulatory T cells (Tregs) that specifically recognize self-antigen. Conventional CD4+ T cells with the same self-antigen specificity remained unresponsive even after Treg ablation. Therefore, the self-antigen-specific CD4+ T cell repertoire plays a regulatory role in limiting tissue damage and autoimmunity during acute injury.
Article
Hematology
Teresa L. Ramos, Sara Bolivar-Wagers, Sujeong Jin, Govindarajan Thangavelu, Federico Simonetta, Po-Yu Lin, Toshihito Hirai, Asim Saha, Brent Koehn, Leon L. Su, Lora K. Picton, Jeanette Baker, Juliane K. Lohmeyer, Megan Riddle, Cindy Eide, Jakub Tolar, Angela Panoskaltsis-Mortari, John E. Wagner, K. Christopher Garcia, Robert S. Nogrin, Bruce R. Blazar
Summary: Expanding regulatory T cells using a novel approach can improve the effectiveness of transplantation and maintain graft-versus-host disease protection and graft-versus-tumor responses.
Article
Cell Biology
Daniele Avancini, Alessandro Testori, Lucia Fresolone, Grazia Andolfi, Michela Vuono, Vittorio Martinelli, Francesca R. Santoni de Sio, Silvia Gregori
Summary: IL-10 induces the generation of tolerogenic dendritic cells (tolDC) from monocytes through the activation of aryl hydrocarbon receptor (AHR). AHR activity downstream of IL-10 signaling is required for the induction of tolerogenic activities in DCs, and this IL-10/AHR genomic signature is active in circulating DCs in healthy individuals. However, in multiple sclerosis patients, an altered IL-10/AHR signature is observed, which correlates with functional defects and reduced frequencies of IL-10-induced tolDCs in vitro and in vivo.
Article
Oncology
Robert J. Harris, Zena Willsmore, Roman Laddach, Silvia Crescioli, Jitesh Chauhan, Anthony Cheung, Anna Black, Jenny L. C. Geh, Alastair D. MacKenzie Ross, Ciaran Healy, Sophia Tsoka, James Spicer, Katie E. Lacy, Sophia N. Karagiannis
Summary: B cells play a key role in anti-tumor immune responses. This study found that patients with melanoma had increased regulatory B cell populations and reduced pro-inflammatory B cell populations compared to healthy volunteers. These B cells interacted with T cells and regulatory T cells, and patient-derived B cells promoted the differentiation of regulatory T cells and sustained the expression of immune factors by autologous T helper cells. The findings suggest the importance of cytokine-expressing B cells in the immune response to melanoma.
Article
Multidisciplinary Sciences
Michael Agrez, Justyna Rzepecka, Darryl Turner, Gavin Knox, Christopher Chandler, Christopher B. Howard, Nicholas Fletcher, Kristofer Thurecht, Stephen Parker, Hayley Gooding, Laura Gallagher
Summary: T cell-dendritic cell interactions play a crucial role in immune responses and autoimmune diseases. A lipidic peptide, IK14004, can modify this interaction and may have therapeutic potential in autoimmune diseases.
SCIENTIFIC REPORTS
(2022)
Article
Surgery
Sharad K. Mittal, WonKyung Cho, Elsayed Elbasiony, Yilin Guan, William Foulsham, Sunil K. Chauhan
Summary: The study showed that CD80 in MSCs plays a crucial role in modulating Treg function. In vitro and in vivo experiments, as well as a mouse transplantation model, demonstrated the impact of CD80 on Tregs.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Biochemistry & Molecular Biology
Hung-Wen Chen, Chia- Lin, Ya-Hui Chuang
Summary: IL-30 treatment reduces activated CD4(+) T cells and regulatory T cells, but does not suppress liver inflammation in the murine model of PBC.
Article
Immunology
Yongsheng Luo, Feifei Luo, Kuanxin Zhang, Shilei Wang, Haojie Zhang, Xianlei Yang, Wenjun Shang, Junxiang Wang, Zhigang Wang, Xinlu Pang, Yonghua Feng, Lei Liu, Hongchang Xie, Guiwen Feng, Jinfeng Li
Summary: Circulating IL-10(+) Breg levels are a more appropriate indicator for assessing resistance to AMR after kidney transplantation compared to Bregs. Kidney B cell and IL-10 infiltration, as well as high expression of CXCL13, were associated with AMR. Furthermore, circulating IL-10(+) Bregs remained elevated during the 90-day post-operation period, contributing to immune homeostasis.
FRONTIERS IN IMMUNOLOGY
(2021)
