Article
Immunology
Dandan Yang, Xueqiang Zhao, Xin Lin
Summary: Bcl10 plays a critical role in the development and function of regulatory T (Treg) cells, deficiency of which leads to impaired development and suppressive function of Treg cells, even causing lethal autoimmunity. Bcl10-deficient Treg cells can undergo conversion into proinflammatory cells and decrease in effector Treg cell populations. The study provides genetic evidence that Bcl10 is essential for Treg cell development and function.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Immunology
Kathryn A. Knoop, Keely G. McDonald, Chyi-Song Hsieh, Phillip Tarr, Rodney D. Newberry
Summary: Atopic disorders are on the rise in Western societies, characterized by immune responses to environmental triggers. Early life exposure to diet and microbes shapes the intestinal Treg population significantly. Tregs developed early in life play a crucial role in restraining systemic inflammatory responses into adulthood.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Giulia Escobar, Katherine Tooley, Joan Pages Oliveras, Linglin Huang, Hanning Cheng, Michelle L. Bookstaver, Camilla Edwards, Eugene Froimchuk, Chang Xue, Davide Mangani, Rajesh K. Krishnan, Natanael Hazel, Carola Rutigliani, Christopher M. Jewell, Luca Biasco, Ana C. Anderson
Summary: TCF1 is essential for priming tumor antigen specific CD8+ T cells and ICB response in poorly immunogenic tumors, but dispensable in highly immunogenic tumors. Improving T cell priming by vaccination or enhancing antigen presentation on tumors can rescue the defective responses of TCF1-deficient CD8+ T cells in poorly immunogenic tumors.
Article
Immunology
Hyunju Oh, Jingyao Zhao, Yenkel Grinberg-Bleyer, Thomas S. Postler, Pingzhang Wang, Sung-Gyoo Park, Raul Rabadan, Matthew S. Hayden, Sankar Ghosh
Summary: This study demonstrates the essential role of PDK1 in both T cell activation and Treg cell suppressive activity, with PDK1 regulating Treg cell gene expression and suppressor function primarily through the NF-κB pathway.
JOURNAL OF IMMUNOLOGY
(2021)
Review
Immunology
Diego Catalan, Miguel Andres Mansilla, Ashley Ferrier, Lilian Soto, Kristine Oleinika, Juan Carlos Aguillon, Octavio Aravena
Summary: Regulatory B cells play a crucial role in maintaining immune tolerance and preventing exacerbated inflammatory responses. In addition to IL-10, other molecules such as IL-35, TGF-beta, and cell surface proteins like CD1d and PD-L1 are utilized by Bregs to regulate immune responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Editorial Material
Immunology
Karoliina Tuomela, Megan K. Levings
Summary: A recent study reveals that lactic acid, through a pH-dependent mechanism, promotes the differentiation of conventional CD4(+) T cells into Tregs, contributing to the accumulation of Tregs within tumors. This finding adds to the understanding of lactic acid's role in maintaining an immunosuppressive tumor microenvironment.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Dermatology
Lazaro Emilio Aira, Gudrun Fiona Debes
Summary: The study found that IL-10(+) Bregs in the skin play a crucial role in suppressing skin inflammation, as a decrease in IL-10(+) Bregs entering the skin leads to exacerbation of inflammation.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Immunology
Rui Dai, Xiaopei Huang, Yiping Yang
Summary: This study demonstrates the critical role of gamma delta T cells in promoting the CD8(+) T cell response to VV infection. Gamma delta T cells are able to present viral antigens and activate CD8(+) T cells, with MyD88 signaling playing a key role in this process. Understanding the regulation of adaptive T cell response by gamma delta T cells may provide insight for the development of more effective vaccine strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Julian Swatler, Laura Turos-Korgul, Marta Brewinska-Olchowik, Sara De Biasi, Wioleta Dudka, Bac Viet Le, Agata Kominek, Salwador Cyranowski, Paulina Pilanc, Elyas Mohammadi, Dominik Cysewski, Ewa Kozlowska, Wioleta Grabowska-Pyrzewicz, Urszula Wojda, Grzegorz Basak, Jakub Mieczkowski, Tomasz Skorski, Andrea Cossarizza, Katarzyna Piwocka
Summary: Leukemic extracellular vesicles play a role in stimulating immunosuppressive Tregs and promoting leukemia growth. The study identifies Rab27a-dependent secretion of leukemic EVs as a potential therapeutic target in myeloid neoplasms.
Article
Multidisciplinary Sciences
Alejandro J. Cagnoni, Maria Laura Giribaldi, Ada G. Blidner, Anabela M. Cutine, Sabrina G. Gatto, Rosa M. Morales, Mariana Salatino, Martin C. Abba, Diego O. Croci, Karina V. Marino, Gabriel A. Rabinovich
Summary: Colorectal cancer is a common malignancy with limited response to immunotherapy, prompting the need for new biomarkers and therapeutic targets. Gal-1, as an endogenous glycan-binding protein, has been found to influence the activity of CD8(+) regulatory T cells in CRC, suggesting a potential immunotherapeutic approach for this disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Faezzah Baharom, Ramiro A. Ramirez-Valdez, Kennedy K. S. Tobin, Hidehiro Yamane, Charles-Antoine Dutertre, Ahad Khalilnezhad, Glennys Reynoso, Vincent L. Coble, Geoffrey M. Lynn, Matthew P. Mule, Andrew J. Martins, John P. Finnigan, Xiao Meng Zhang, Jessica A. Hamerman, Nina Bhardwaj, John S. Tsang, Heather D. Hickman, Florent Ginhoux, Andrew S. Ishizuka, Robert A. Seder
Summary: The study demonstrates that using a self-assembling nanoparticle vaccine and adjuvant can expand stem-like CD8(+) T cells, optimize anti-tumor immunity, and enhance the strength and effectiveness of the anti-tumor response.
Article
Multidisciplinary Sciences
Nadine Kamenjarin, Katrin Hodapp, Felix Melchior, Gregory Harms, Ann- Kathrin Hartmann, Joschka Bartneck, Sabine Muth, Verena K. Raker, Christian Becker, Anna Brand, Bjorn E. Clausen, Markus P. Radsak, Hansjorg Schild, Hans Christian Probst
Summary: Tissue-resident memory CD8+ T cells (TRM) in the skin require epidermal Langerhans cells, which cross-present keratinocyte-derived antigens, for their reactivation to provide protection against reinfection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Jemma Nicholls, Benjamin Cao, Laetitia Le Texier, Laura Yan Xiong, Christopher R. Hunter, Genesis Llanes, Ethan G. Aguliar, Wayne A. Schroder, Simon Phipps, Jason P. Lynch, Huimin Cao, Shen Y. Heazlewood, Brenda Williams, Andrew D. Clouston, Christian M. Nefzger, Jose M. Polo, Susan K. Nilsson, Bruce R. Blazar, Kelli P. A. MacDonald
Summary: BM-Treg and pTreg exhibit distinct characteristics, including differential expression of chemokine receptors, transcription factors, and cell cycle control genes. BM-Treg show unique properties and are functionally and phenotypically different from splenic Treg.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Magdalena Piotrowska, Mateusz Gliwinski, Piotr Trzonkowski, Dorota Iwaszkiewicz-Grzes
Summary: Regulatory T cells (Tregs) play a critical role in the immune system by exerting suppressive functions, and disturbances in their function can lead to autoimmune dysregulation. Apart from Foxp3, other genes are involved in Tregs development and function. Epigenetic changes, specifically DNA methylation, are believed to be crucial in determining Tregs function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Maximilian Haist, Henner Stege, Stephan Grabbe, Matthias Bros
Summary: Immunotherapy has shown benefits for advanced cancer patients, but many still do not respond to treatment. The accumulation of immunosuppressive cell populations like MDSC and Treg in the tumor microenvironment contributes to immune resistance and limits the effectiveness of immunotherapy.
Letter
Oncology
Elizabeth F. McInnes, David K. Meyerholz, Mark J. Arends
JOURNAL OF PATHOLOGY
(2023)
Article
Anesthesiology
Joseph B. Lesnak, David S. Nakhla, Ashley N. Plumb, Alexandra McMillan, Sanjib Saha, Nikesh Gupta, Yan Xu, Pornpoj Phruttiwanichakun, Lynn Rasmussen, David K. Meyerholz, Aliasger K. Salem, Kathleen A. Sluka
Summary: Chronic pain is a major health problem that affects disability and quality of life. Current treatments for chronic pain are ineffective, so there is a need for new analgesics. In this study, the researchers tested the efficacy of selective androgen receptor modulators (SARMs) in a mouse model of muscle pain. They found that SARMs alleviated muscle hyperalgesia in both male and female mice, and this effect was mediated through androgen receptors. The SARM-loaded microparticles released the drug for a sustained period and did not produce toxic or rewarding effects. These findings suggest that SARM-loaded microparticles could be a potential therapy for chronic muscle pain.
Article
Multidisciplinary Sciences
Lalita Mazgaeen, Matthew Yorek, Saurabh Saini, Peter Vogel, David K. Meyerholz, Thirumala-Devi Kanneganti, Prajwal Gurung
Summary: Mice with a specific amino acid substitution in SHP1 protein (Ptpn6(spin) mice) develop an autoinflammatory disease. When Ptpn6(spin) bone marrow cells are transferred into Cd47-deficient mice, marked weight loss and death occur. The study suggests that gut leakage caused by pathogenic neutrophils may contribute to the morbidity and mortality in Cd47(-/-) mice receiving Ptpn6(spin) cells. IL-1 blockade with anakinra can rescue the disease phenotype.
Editorial Material
Medicine, General & Internal
David K. Meyerholz
Article
Biochemistry & Molecular Biology
Athmane Teghanemt, Kara Misel-Wuchter, Jace Heath, Andrew Thurman, Priyanjali Pulipati, Garima Dixit, Ramasatya Geesala, David K. Meyerholz, Thorsten Maretzky, Alejandro Pezzulo, Priya D. Issuree
Summary: Regulatory T (T reg) cells are vital in maintaining tolerance and preventing fatal autoimmunity. This study reveals the importance of Tet enzymes and DNA demethylation in promoting Treg cell differentiation in the thymus. Tet3 is specifically involved in the development of CD4 single-positive thymocytes and plays a critical role in TCR-dependent IL-2 production, which is essential for chromatin remodeling and the upregulation of FoxP3.
Editorial Material
Pathology
David K. Meyerholz
VETERINARY PATHOLOGY
(2023)
Article
Biology
David K. Meyerholz, Mariah R. Leidinger, J. Adam Goeken, Thomas R. Businga, Sebastian Vizuett, Allison Akers, Idil Evans, Yan Zhang, John F. Engelhardt
Summary: Our objective was to qualify MUC5AC and MUC5B immunohistochemical techniques to provide a useful tool for studying mucin tissue in CF and other ferret models. Results showed that MUC5AC and MUC5B mucins were most commonly detected in large airways and least in small airways, consistent with goblet cell density in airway surface epithelia. We also found that stomach tissues were enriched in MUC5AC and gallbladder tissues were enriched in MUC5B, similar to human tissues. Qualified techniques for MUC5AC and MUC5B immunohistochemistry will be valuable for mucin tissue studies.
BMC RESEARCH NOTES
(2023)
Article
Chemistry, Multidisciplinary
Sudartip Areecheewakul, Andrea Adamcakova-Dodd, Zeb R. Zacharias, Xuefang Jing, David K. Meyerholz, Kevin L. Legge, Jon C. D. Houtman, Patrick T. O'Shaughnessy, Peter S. Thorne, Aliasger K. Salem
Summary: This study investigated the immunomodulatory effects of inhalation exposure to copper oxide nanoparticles (CuO NPs) in different immune conditions. The results showed that CuO NP exposure decreased T(H)1 and T(H)2 cells and increased T-bet(+) Treg cells in healthy mice. However, CuO NP inhalation exposure resulted in decreased T(H)2 responses and increased T-bet(+) Treg cells in mice with house dust mite (HDM) asthma, and increased T(H)2 cells in AIT-treated asthmatic mice.
Article
Oncology
Jordan L. Kohlmeyer, Joshua J. Lingo, Courtney A. Kaemmer, Amanda Scherer, Akshaya Warrier, Ellen Voigt, Juan A. Raygoza Garay, Gavin R. Mcgivney, Qierra R. Brockman, Amy Tang, Ana Calizo, Kai Pollard, Xiaochun Zhang, Angela C. Hirbe, Christine A. Pratilas, Mariah Leidinger, Patrick Breheny, Michael S. Chimenti, Jessica C. Sieren, Varun Monga, Munir R. Tanas, David K. Meyerholz, Benjamin W. Darbro, Rebecca D. Dodd, Dawn E. Quelle
Summary: Targeting CDK4/6 and MEK inhibitors in MPNSTs can synergistically activate tumor suppressor genes, induce cell death, and reduce tumor survival, while CDK4/6-MEK inhibition can enhance the efficacy of anti-PD-L1 therapy.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Yunchen Wu, Yudan He, Chen Liu, Charlotte Ehle, Aishwarya Iyer-Bierhoff, Bing Liu, Thorsten Heinzel, Shaojun Xing
Summary: Sepsis is a life-threatening condition caused by excessive inflammation in response to an infection. Histone deacetylase inhibitors (HDACi) have been suggested as potential anti-inflammatory agents for sepsis treatment. In this study, the effects of SAHA, a HDACi, were investigated in a mouse model of endotoxemia. The results showed reduced inflammation and improved survival rates in mice, possibly through the inhibition of LDHA activity and inflammasome activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Feng Yuan, Grace N. Gasser, Evan Lemire, Daniel T. Montoro, Karthik Jagadeesh, Yan Zhang, Yifan Duan, Vitaly Ievlev, Kristen L. Wells, Pavana G. Rotti, Weam Shahin, Michael Winter, Bradley H. Rosen, Idil Evans, Qian Cai, Miao Yu, Susan A. Walsh, Michael R. Acevedo, Darpan N. Pandya, Vamsidhar Akurathi, David W. Dick, Thaddeus J. Wadas, Nam Soo Joo, Jeffrey J. Wine, Susan Birket, Courtney M. Fernandez, Hui Min Leung, Guillermo J. Tearney, Alan S. Verkman, Peter M. Haggie, Kathleen Scott, Douglas Bartels, David K. Meyerholz, Steven M. Rowe, Xiaoming Liu, Ziying Yan, Adam L. Haber, Xingshen Sun, John F. Engelhardt
Summary: This study demonstrates the crucial role of ionocytes in controlling airway surface liquid volume and mucociliary clearance through CFTR-dependent ion transport. The creation of conditional genetic ferret models enables the study of ionocyte biology and function, providing insights into human health and disease that have greater evolutionary conservation compared to traditional rodent models.
Article
Multidisciplinary Sciences
Pengfei Li, Biyun Xue, Nicholas J. Schnicker, Lok- Yin Roy Wong, David K. Meyerholz, Stanley Perlman
Summary: The unique region (SUD) in the nonstructural protein Nsp3 of SARS-CoV-2 plays an important role in enhancing viral translation. The study identified a attenuated virus with a mutation in the linker region of Nsp3 and a compensatory mutation in the nucleocapsid protein (N) that restored virulence, revealing the impact of Nsp3-N interactions on virus replication and pathogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Microbiology
Lok-Yin Roy Wong, Abby Odle, Emma Luhmann, Douglas C. Wu, Yiquan Wang, Qi Wen Teo, Celeste Ptak, Alan Sariol, Shea Lowery, Matthias Mack, David K. Meyerholz, Nicholas C. Wu, Lilliana Radoshevich, Stanley Perlman
Summary: The internal proteins 8b and 9b of MERS-CoV and SARS-CoV-2 have different roles in mediating pathogenesis in infected animals. MERS-CoV lacking protein 8b expression is more virulent, while SARS-CoV-2 lacking protein 9b expression is attenuated. Additionally, mice infected with MERS-CoV lacking protein 8b expression showed increased levels of interferon and immune cell infiltration.
Article
Veterinary Sciences
David Diaz-Reganon, Vojtech Gabriel, Vanessa Livania, Dongjie Liu, Basant H. Ahmed, Addison Lincoln, Hannah Wickham, Abigail Ralston, Maria M. Merodio, Dipak K. Sahoo, Christopher Zdyrski, David K. Meyerholz, Jonathan P. Mochel, Karin Allenspach
Summary: Recent studies have highlighted the importance of intestinal mucosal changes in chronic enteropathies. This study examined the morphological changes in enterocytes and the ratio of goblet cells to enterocytes in dogs with chronic enteropathies. The results showed significant alterations in enterocyte size and a decreased goblet cell-to-enterocyte ratio in the colon, similar to celiac disease in humans.
VETERINARY SCIENCES
(2023)
Article
Multidisciplinary Sciences
Abigail R. Gress, Christine E. Ronayne, Joshua M. Thiede, David K. Meyerholz, Samuel Okurut, Julia Stumpf, Tailor V. Mathes, Kenneth Ssebambulidde, David B. Meya, Fiona V. Cresswell, David R. Boulware, Tyler D. Bold
Summary: The OX40 protein is proposed as a marker for recently activated CD4 T cells at the infection site in tuberculosis, indicating its potential as a target for immunotherapy.
NATURE COMMUNICATIONS
(2023)