Review
Immunology
Joshua M. Moreau, Maria Velegraki, Chelsea Bolyard, Michael D. Rosenblum, Zihai Li
Summary: TGF-beta 1 plays a crucial role in the development and function of T-reg, although its pleiotropic and context-dependent activity makes it complicated.
SCIENCE IMMUNOLOGY
(2022)
Article
Biology
Margaret H. O'Connor, Roshell Muir, Marita Chakhtoura, Michael Fang, Eirini Moysi, Susan Moir, Alison J. Carey, Alyssa Terk, Carmen N. Nichols, Talibah Metcalf, Constantinos Petrovas, Mark J. Cameron, Virginie Tardif, Elias K. Haddad
Summary: Researchers report a new population of Innate Lymphoid Cells in human tonsils and lymph nodes that inhibit the functional interaction of follicular helper T cells and germinal center B cells. They show that this cell population is expanded under chronic HIV infection, resulting in decreased antibody production, suggesting a potential role for these cells in diseases with dysregulated immune responses.
COMMUNICATIONS BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Mai Fujiwara, Radhika Raheja, Lucien P. Garo, Amrendra K. Ajay, Ryoko Kadowaki-Saga, Sukrut H. Karandikar, Galina Gabriely, Rajesh Krishnan, Vanessa Beynon, Anu Paul, Amee Patel, Shrishti Saxena, Dan Hu, Brian C. Healy, Tanuja Chitnis, Roopali Gandhi, Howard L. Weiner, Gopal Murugaiyan
Summary: This study reveals the crucial role of microRNA-92a (miR-92a) in central nervous system autoimmune diseases. Elevated miR-92a level in experimental autoimmune encephalomyelitis (EAE) contributes to the progression of the disease, while loss of miR-92a attenuates EAE. Mechanistically, miR-92a restricts the induction and suppressive capacity of regulatory T cells (Tregs), while supporting the responses of inflammatory T cells (Th17) by targeting the transcription factor Foxo1. Additionally, miR-92a inhibitor therapy improves EAE by enhancing Treg responses and suppressing inflammatory T cell responses.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Editorial Material
Biochemistry & Molecular Biology
Kelly A. Speer
Summary: Parasitic and parasitoid organisms rely on chemical cues to locate a host. Recent research suggests that the microbiome can emit volatile organic compounds that attract or repel parasites. This innovative mechanism changes our understanding of host-parasite coevolution and highlights the role of the microbiome as a third actor in this interaction.
Review
Biochemistry & Molecular Biology
Zhuo Chen, Hanjie Yu, Xiangqin Chen, Wentian Chen, Wanghua Song, Zheng Li
Summary: TGF-beta superfamily members play important roles in various diseases, and glycosylation modification is involved in the regulation of TGF-beta signaling pathway. There is a complex mutual regulation between glycosylation and TGF-beta signaling, which affects biological processes.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Review
Immunology
Karthik Chandiran, Linda S. Cauley
Summary: Cytotoxic T lymphocytes (CTLs) are crucial for defense against intracellular pathogens and tumors, requiring efficient migration to locate and destroy infected cells in different regions of the body. The transforming growth factor-beta (TGF-beta) and canonical SMAD-dependent signaling pathways are essential for coordinating changes in homing receptor expression and ensuring successful migration of CTLs.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Microbiology
Emily DeMichele, Olivia Sosnowski, Andre G. Buret, Thibault Allain
Summary: Body tissues can experience temporary hypoxia due to variations in oxygen levels. The hypoxic response is regulated by hypoxia-inducible factor (HIF), which influences cellular metabolism, immune responses, barrier integrity, and microbiota. Recent studies have investigated the response to hypoxia during various infections, but the role of HIF activation in protozoan parasitic infections is still poorly understood. Evidence suggests that protozoa can activate HIF and target genes in the host, affecting their pathogenicity. This review focuses on the hypoxic response to protozoan infections and its impact on host immune responses.
Review
Cell Biology
Sepiso K. Masenga, Bislom C. Mweene, Emmanuel Luwaya, Lweendo Muchaili, Makondo Chona, Annet Kirabo
Summary: The development of antiretroviral drugs (ARVs) is a significant achievement in managing HIV infections by suppressing viral activity and extending lifespan. However, the success of HIV in evading the immune system has hindered the discovery of an effective treatment for four decades. Understanding the molecular interaction between HIV and host cells is crucial for developing preventive and curative therapies. This review highlights the inherent mechanisms of HIV, such as targeting CD4(+) lymphocytes, downregulating MHC class I and II, antigenic variation, and minimizing antibody access, which collectively render the immune system ineffective.
Article
Biochemistry & Molecular Biology
Yanan Min, Long Hao, Xinguang Liu, Shuai Tan, Hui Song, Hao Ni, Zi Sheng, Natalie Jooss, Xuena Liu, Rickard E. Malmstrom, Yang Sun, Jianguo Liu, Hua Tang, Hao Zhang, Chunhong Ma, Jun Peng, Ming Hou, Nailin Li
Summary: This study investigated the mechanisms underlying the regulation of effector responses of naive CD4(+) T (Tn) cells by platelets. The results showed that platelets exert sophisticated regulation on various types of T helper cells and regulatory T cells in a time-, concentration-, and organ-dependent manner, in cooperation with transforming growth factor beta (TGF beta) and platelet factor 4 (PF4). This study highlights the importance of platelet-targeted interventions for T cell immunity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Medicinal
Manman Ma, Xiaohua Wang, Xiaohui Liu, Yang Han, Yanhui Chu, Yanzhong Guan, Haifeng Liu
Summary: A novel tT beta RII variant, Z-tT beta RII, was designed by fusing the PDGF beta receptor-specific affibody Z(PDGF beta R) to the N-terminus of tT beta RII. Z-tT beta RII exhibited superior specific fibrotic liver-targeting potential and stronger anti-fibrotic effects in vitro and in vivo. It also showed no significant sign of potential side effects in other vital organs in liver fibrotic mice, making it a potential candidate for targeted therapy for liver fibrosis.
ARCHIVES OF PHARMACAL RESEARCH
(2023)
Article
Medicine, Research & Experimental
Kang Mi Lee, Qiang Fu, Guoli Huai, Kevin Deng, Ji Lei, Lisa Kojima, Divyansh Agarwal, Peter van Galen, Shoko Kimura, Naoki Tanimine, Laura Washburn, Heidi Yeh, Ali Naji, Charles G. Rickert, Christian LeGuern, James F. Markmann
Summary: B lymphocytes play important roles in adaptive immunity and self-tolerance. Activated B cells through TLR4/TLR9 receptors acquire regulatory properties, inhibiting T cell proliferation and preventing allograft rejection.
Review
Biochemistry & Molecular Biology
Xinyi Wang, Ting Liu, Yifei Huang, Yifeng Dai, Hui Lin
Summary: Fibrosis is a complex abnormal healing process that involves multiple signaling pathways, with the TGF-beta signaling pathway playing a central role. TGF-beta precisely regulates fibrogenesis by controlling gene transcription and translation, and SUMOylation has been identified as a key player in this process, providing potential therapeutic strategies for fibrosis.
Article
Immunology
Ha-Yeon Song, Fengjia Chen, Hae Ran Park, Jeong Moo Han, Hyun Jung Ji, Eui-Baek Byun, Yeongkag Kwon, Min-Kyu Kim, Ki Bum Ahn, Ho Seong Seo
Summary: Low-dose radiation therapy (LDRT) can effectively reduce the severity of coronavirus disease (COVID-19) and other cases of viral pneumonia. In this study, the molecular mechanism underlying immunological alterations in influenza pneumonia after LDRT was investigated.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Mengze Lyu, Hiroaki Suzuki, Lan Kang, Fabrina Gaspal, Wenqing Zhou, Jeremy Goc, Lei Zhou, Jordan Zhou, Wen Zhang, Zeli Shen, James G. Fox, Robbyn E. Sockolow, Terri M. Laufer, Yong Fan, Gerard Eberl, David R. Withers, Gregory F. Sonnenberg
Summary: This study reveals a critical pathway that controls the fate of inflammatory or tolerogenic T cell responses to microbial colonization of the mammalian intestine. By profiling all ROR gamma t(+) immune cells at single-cell resolution, the researchers found a dominant presence of T regulatory cells and ILC3s in the intestine-draining lymph nodes of mice. These ILC3s promote the formation of microbiota-specific ROR gamma t(+) T-reg cells and prevent their expansion as inflammatory T helper 17 cells through antigen presentation, alpha V integrin, and competition for interleukin-2. Single-cell analyses also suggest impaired interactions between ILC3s and ROR gamma t(+) T-reg cells in inflammatory bowel disease.
Article
Biochemistry & Molecular Biology
Fuensanta Gomez-Bernal, Juan Carlos Quevedo-Abeledo, Maria Garcia-Gonzalez, Yolanda Fernandez-Cladera, Agustin F. Gonzalez-Rivero, Antonia de Vera-Gonzalez, Candelaria Martin-Gonzalez, Miguel A. Gonzalez-Gay, Ivan Ferraz-Amaro
Summary: This study aimed to investigate the relationship between serum levels of transforming growth factor beta 1 (TGF-β1) and disease characteristics, activity, damage, or severity in patients with systemic lupus erythematosus (SLE). The results showed that TGF-β1 serum levels were associated with disease severity and activity, with ocular and cardiovascular manifestations positively correlated, while gastrointestinal and musculoskeletal involvements negatively correlated with circulating TGF-β1 levels.
Article
Biochemistry & Molecular Biology
Emma Proics, Marion David, Majid Mojibian, Madeline Speck, Nadia Lounnas-Mourey, Adeline Govehovitch, Wissam Baghdadi, Justine Desnouveaux, Herve Bastian, Laura Freschi, Geoffrey Privat, Cedric Pouzet, Mauro Grossi, Pierre Heimendinger, Tobias Abel, David Fenard, Megan K. Levings, Francois Meyer, Celine Dumont
Summary: This publication reports the preclinical characterization of Tregs transduced with a CAR lentiviral vector. The results demonstrated the specificity, immunosuppressive function, and safety of the transduced Tregs. The study also showed that the transduced Tregs effectively prevented graft-versus-host disease in mice and remained stable without switching to a proinflammatory phenotype. Furthermore, concomitant tacrolimus did not impair the survival or inhibitory function of the transduced Tregs.
Review
Endocrinology & Metabolism
Adam Ramzy, Paul J. Belmonte, Mitchell J. S. Braam, Shogo Ida, Emily M. Wilts, Megan K. Levings, Alireza Rezania, Timothy J. Kieffer
Summary: Insulin injections have saved many lives, but glycemic instability remains a challenge for people with diabetes. Islet transplantation research suggests that replacing insulin-producing beta cells can restore normal blood sugar levels. Pluripotent stem cells could provide an unlimited supply of beta cells, but more research and development is needed.
Article
Cell Biology
Laura Cook, John Zaunders, Nabila Seddiki, David van Bockel, Anthony D. Kelleher, C. Mee Ling Munier
Summary: The study aims to extend the utility of activation induced marker (AIM) assays for tracking and quantifying pre-activation defined cell populations within T-cell memory responses. By labeling cells with different fluorescent dyes and performing AIM assays, the specific cell populations within antigen stimulated responses can be tracked.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Immunology
Dominic A. Boardman, May Q. Wong, William D. Rees, Dan Wu, Megan E. Himmel, Paul C. Orban, Jens Vent-Schmidt, Nicholas C. Zachos, Theodore S. Steiner, Megan K. Levings
Summary: Regulatory T cell (Treg) therapy is a promising strategy for treating inflammatory bowel disease (IBD). A novel chimeric antigen receptor (CAR) specific for flagellin derived from Escherichia coli H18 (FliC) was developed to confer FliC-specificity to human Tregs. FliC-CAR Tregs showed specificity and functionality, and demonstrated potential in treating IBD by suppressing inflammation and promoting the establishment of colon-derived epithelial cell monolayers.
JOURNAL OF AUTOIMMUNITY
(2023)
Review
Microbiology
Abbas Yadegar, Sepideh Pakpoor, Fathima F. Ibrahim, Ali Nabavi-Rad, Laura Cook, Jens Walter, Anna M. Seekatz, Karen Wong, Tanya M. Monaghan, Dina Kao
Summary: Fecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection (rCDI), but the mechanisms behind its efficacy are not fully understood. This paper provides an overview of rCDI pathogenesis and discusses potential mechanisms of action, including microbial, metabolic, immunological, and epigenetic mechanisms. The authors also outline research gaps and recommend methodological improvements for future studies to better understand and develop targeted therapies to replace FMT.
CELL HOST & MICROBE
(2023)
Review
Immunology
Martin L. Mak, Kyle T. Reid, Sarah Q. Crome
Summary: In this review, the authors explore the protective and pathogenic functions of innate lymphoid cell (ILC) family members in transplantation. They also discuss the potential advantages of harnessing or targeting ILCs in transplantation and the challenges limiting clinical translation. ILCs are a family of lymphocytes that play essential roles in tissue homeostasis and immunity, with subsets of ILCs either promoting or inhibiting immune tolerance. Understanding the functions of ILCs in transplantation is still in the early stages, but they have the potential to contribute to immune tolerance or rejection.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Review
Cell Biology
Chad Poloni, Cole Schonhofer, Sabine Ivison, Megan K. Levings, Theodore S. Steiner, Laura Cook
Summary: Activation-induced marker (AIM) assays are a useful and fast method for detecting antigen-specific T-cells. This method involves incubating whole blood or peripheral blood mononuclear cells with antigens, leading to the upregulation of activation markers on T-cells. The AIM assays can be used to analyze T-cell frequency, phenotype, and function without knowing the exact antigenic peptides and MHC restriction elements.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Review
Immunology
Karoliina Tuomela, Kevin Salim, Megan K. Levings
Summary: Regulatory T cells (Tregs) have been recognized as critical cells for immune homeostasis regulation. The development of designer Tregs has gone through three eras: FOXP3 engineering, antigen-specificity, and advanced genome-editing techniques, providing new opportunities for treating immune-mediated diseases.
IMMUNOLOGICAL REVIEWS
(2023)
Editorial Material
Cell Biology
Laura Cook, C. Mee Ling Munier
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Laura Cook, May Q. Wong, William D. Rees, Alana Schick, Daniel J. Lisko, Genelle R. Lunken, Xiaojiao Wang, Hannah Peters, Laura Oliveira, Torey Lau, Regan Mah, Brian Bressler, Megan K. Levings, Theodore S. Steiner
Summary: IBD patients may experience undiagnosed C. difficile infections due to underlying intestinal dysbiosis, resulting in impaired toxin-specific immunity and increased inflammatory T cell responses towards commensal bacteria.
INFLAMMATORY BOWEL DISEASES
(2023)
Article
Immunology
Esther Bernaldo-de-Quiros, Manuela Camino, Marta Martinez-Bonet, Juan Miguel Gil-Jaurena, Nuria Gil, Diana Hernandez-Florez, Maria Eugenia Fernandez-Santos, Laura Butragueno, I. Esme Dijke, Megan K. Levings, Lori J. West, Marjorie Pion, Rafael Correa-Rocha
Summary: This study developed a new approach to obtain large quantities of high-purity Tregs from routine surgeries, which could be used for cellular therapy to prevent transplant rejection. The initial results of the clinical trial showed that the administration of thyTregs in infants undergoing heart transplantation had no adverse effects and maintained a stable Treg frequency in the peripheral blood.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Immunology
Cara E. Ellis, Majid Mojibian, Shogo Ida, Vivian C. W. Fung, Sos Skovso, Emma McIver, Shannon O'Dwyer, Travis D. Webber, Mitchell J. S. Braam, Nelly Saber, Shugo Sasaki, Francis C. Lynn, Timothy J. Kieffer, Megan K. Levings
Summary: This study used A2-CAR T cells to investigate the rejection of insulin-producing cells and successfully addressed the issue of complications from xenogeneic graft-versus-host disease.
Article
Immunology
Ji-Young V. Kim, Sara Assadian, Zsuzsanna Hollander, Paloma Burns, Casey P. Shannon, Karen Lam, Mustafa Toma, Andrew Ignaszewski, Ross A. Davies, Diego Delgado, Haissam Haddad, Debra Isaac, Daniel Kim, Alice Mui, Miroslaw Rajda, Lori West, Michel White, Shelley Zieroth, Paul A. Keown, W. Robert McMaster, Raymond T. Ng, Bruce M. McManus, Megan K. Levings, Scott J. Tebbutt
Summary: This study demonstrates that gene expression associated with CD4+ Tconv and Treg can identify patients at risk of ACR. Complementing HEARTBiT with TGS improves the classification of ACR.
Article
Medicine, Research & Experimental
Isaac Rosado-Sanchez, Manjurul Haque, Kevin Salim, Madeleine Speck, Vivian C. W. Fung, Dominic A. Boardman, Majid Mojibian, Giorgio Raimondi, Megan K. Levings
Summary: Tregs expressing chimeric antigen receptors (CAR-Tregs) were studied to understand the relationship between CAR structure and Treg function. CD28-encoding CARs showed advantages in xenogeneic, immunodeficient mice, but the interactions with antigen-presenting cells (APCs) and donor specific antibodies were not fully represented. In vitro, CD28-encoding CARs had superior antigen-specific suppression, proliferation, and cytokine production. However, in vivo, Tregs expressing CARs encoding CD28, ICOS, programmed cell death 1, and GITR extended skin allograft survival, while CARs encoding 4-1BB or OX40 did not. Analysis of a CAR encoding CD3 zeta but no costimulatory domain revealed that exogenous costimulation from APCs can compensate for the lack of a CAR-encoded CD28 domain. This study has important implications for the design of CARs for clinical use in Tregs.
Article
Medicine, Research & Experimental
Justin A. Spanier, Vivian Fung, Christine M. Wardell, Mohannad H. Alkhatib, Yixin Chen, Linnea A. Swanson, Alexander J. Dwyer, Matthew E. Weno, Nubia Silva, Jason S. Mitchell, Paul C. Orban, Majid Mojibian, C. Bruce Verchere, Brian T. Fife, Megan K. Levings
Summary: Engineering Tregs with specific recognition for islet antigens using a chimeric antigen receptor (CAR) is a promising therapeutic approach for preventing autoimmune diabetes.
JOURNAL OF CLINICAL INVESTIGATION
(2023)