Article
Immunology
Yvelise Barrios, Andres Franco, Inmaculada Sanchez-Machin, Paloma Poza-Guedes, Ruperto Gonzalez-Perez, Victor Matheu
Summary: Specific spike DTH test shows high concordance with anti-RBD-IgG in identifying COVID-19 patients and has a high specificity in non-sick individuals. It provides more stable results over time compared to specific anti-RBD-IgG testing.
CLINICAL IMMUNOLOGY
(2021)
Review
Genetics & Heredity
Yueran Li, Pooja Deshpande, Rebecca J. Hertzman, Amy M. Palubinsky, Andrew Gibson, Elizabeth J. Phillips
Summary: Adverse drug reactions, particularly delayed hypersensitivity reactions, are T-cell mediated and associated with human leukocyte antigen risk alleles. However, screening implementation is hindered by limited negative and positive predictive values. Other factors contributing to risk of severe T-cell-mediated DHRs include drug metabolism variation and T-cell receptor specificity. It is recognized that susceptibility to DHRs is not solely determined by genetics, but also influenced by therapeutic interventions and epigenetic modifications.
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Svitlana Skoroplyas, Ondrej Vasicek, Michaela Chorvatova, Petra Dad'ova, Katerina Lehka, Lukas Kubala
Summary: Pseurotin D has the potential to inhibit DTH reaction through inhibiting the activation and differentiation of both T cells and B cells.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Review
Oncology
Ines Roger, Paula Montero, Martin Perez-Leal, Javier Milara, Julio Cortijo
Summary: The clinical practice faces the problem of delayed-type hypersensitivity (DTH) caused by various drugs, especially in antineoplastic treatments. DTH reactions can range from mild self-limiting maculopapular eruptions to severe Stevens-Johnson Syndrome, resulting in worsened patient quality of life. Apart from impacting patients, these reactions also lead to economic losses due to drug withdrawal and high hospitalization costs. However, there is currently no standard in vitro or in vivo method to evaluate the sensitizing potential of drugs in preclinical studies. This review aims to comprehensively evaluate in vitro and in vivo methods for detecting DTH and testing antineoplastic hypersensitivity reactions caused by different antineoplastic families.
Article
Immunology
Alycia P. Fratzke, Anthony E. Gregory, Erin J. van Schaik, James E. Samuel
Summary: Q-VAX (R), a vaccine for Q fever, provides long-term protection but can cause reactions in sensitized individuals, limiting its use outside Australia. Studying different mouse strains revealed that the reactions to C. burnetii whole cell vaccine are consistent with a Th1 delayed-type hypersensitivity response.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell & Tissue Engineering
Ji Chen, Chen-Xi Zheng, Yan Jin, Cheng-Hu Hu
Summary: Type 2 diabetes mellitus (T2DM) poses a major threat to global public health, with immune dysfunction recognized as a crucial contributor to its pathogenesis. Mesenchymal stromal cells (MSCs) have emerged as promising therapeutic agents for T2DM, with their immunomodulatory effects mediated through paracrine mechanisms and extracellular vesicles (EVs). Preclinical studies have shown the benefits of MSCs in improving islet function and insulin resistance, while clinical trials have further supported their therapeutic potential for T2DM.
Article
Medicine, General & Internal
Nikita Jhawar, Juan Cardenas Rosales, Alexei Gonzalez-Estrada
Summary: Since the emergency authorization of SARS-CoV-2 vaccines, research has been conducted on managing allergic reactions to the vaccines. Anaphylaxis and benign cutaneous reactions have been reported, with rare cases of rash and atopy occurring at sites apart from the injection site. A unique case of delayed benign cutaneous hypersensitivity in the lower extremity after upper-extremity administration of an mRNA SARS-CoV-2 vaccine is discussed, along with management strategies for similar vaccine-induced hypersensitivity reactions.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Allergy
Ana Copaescu, Effie Mouhtouris, Sara Vogrin, Fiona James, Kyra Y. L. Chua, Natasha E. Holmes, Abby Douglas, Monica A. Slavin, Heather Cleland, Celia Zubrinich, Ar Kar Aung, Michelle S. Y. Goh, Elizabeth J. Phillips, Jason A. Trubiano
Summary: This study aimed to determine whether the combination of skin testing and/or IFN-g enzyme-linked immunoSpot assay (ELI Spot) can aid diagnosis of delayed immune-mediated adverse drug reactions. The results demonstrated that using in vivo testing in combination with ex vivo testing can enhance the diagnostic approach in these severe phenotypes by assisting with the identification of possible culprit antibiotics.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2021)
Article
Medicine, Research & Experimental
Chandan Sona, Yu-Te Yeh, Andreas Patsalos, Laszlo Halasz, Xin Yan, Natalia L. Kononenko, Laszlo Nagy, Matthew N. Poy
Summary: Through single-cell RNA sequencing analysis, this study found increased CADM1(+) cells adjacent to CD8(+) T cells in the islets of individuals with T1D and those who were autoantibody-positive, indicating that CADM1-mediated intercellular contact may facilitate the infiltration of cytotoxic T lymphocytes and could serve as a potential therapeutic target for preventing T1D pathogenesis.
Article
Chemistry, Medicinal
Ines Roger, Paula Montero, Antonio Garcia, Javier Milara, Pilar Ribera, Jose Alejandro Perez-Fidalgo, Julio Cortijo
Summary: Delayed-type hypersensitivity (DTH) is a common reaction caused by various drugs, especially antineoplastic drugs, which may affect patients' quality of life. However, there is currently a lack of standardized methods for evaluating the sensitizing potential of drugs in the preclinical phase. This study aimed to adapt in vitro techniques to predict the sensitizing potential of antineoplastic agents and discovered that inhibition of the VEGFR1 pathway may be a potential trigger of DTH.
Article
Immunology
Patrycja M. Topczewska, Zoe A. Rompe, Manuel O. Jakob, Anton Stamm, Pierre S. Leclere, Alexandra Preusser, Claudia U. Duerr, Linda Marie Laura Thole, Katja Kotsch, David Artis, Christoph S. N. Klose
Summary: Type 2 immune responses at mucosal barriers are regulated by rapidly secreted cytokines called alarmins, such as IL-33, IL-25 and TSLP. These alarmins are secreted by stromal and epithelial cells in tissues and play roles in chronic inflammatory diseases and resistance against worm infections. The receptors for alarmins are expressed by immune cells, including group 2 innate lymphoid cells (ILC2s), which produce type 2 cytokines and are linked to atopic diseases and anti-worm immunity. However, the precise contribution of the IL-33 receptor signals for ILC2 activation still needs further investigation. This study used a mouse model to specifically delete the IL-33 receptor subunit ST2 in ILC2s and found that ST2-deficient ILC2s were unresponsive to IL-33 but still responded to IL-25. ST2-deficient ILC2s produced limited amounts of IL-5 and IL-13 and were unable to support eosinophil homeostasis. Additionally, they could not expand and promote the recruitment of eosinophils during allergic lung inflammation or mount an effective type 2 immune response against worm infections. Therefore, this study highlights the importance of cell-intrinsic ST2 signals for proper activation of ILC2s and initiation of type 2 immunity.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Mu-Tzu Chu, Wan-Chun Chang, Shih-Cheng Pao, Shuen-Iu Hung
Summary: Drug hypersensitivity reactions can be immediate or delayed. Delayed drug hypersensitivity is mainly caused by T lymphocyte recognition of drug antigens and cell activation. This type of hypersensitivity can have various clinical presentations ranging from mild reactions to severe cutaneous adverse reactions. Common culprits of delayed drug hypersensitivity include anti-epileptics, antibiotics, anti-gout agents, and anti-viral drugs. The pathogenesis involves molecular recognition, genetic susceptibility, and immune mediators.
Article
Microbiology
Chris D. Lauruschkat, Sonja Etter, Elisabeth Schnack, Frank Ebel, Sascha Schaeuble, Lukas Page, Dana Rumens, Mariola Dragan, Nicolas Schlegel, Gianni Panagiotou, Olaf Kniemeyer, Axel A. Brakhage, Hermann Einsele, Sebastian Wurster, Juergen Loeffler
Summary: Occupational mold exposure in agricultural workers, particularly organic farmers, leads to higher Th-cell responses to Aspergillus antigens, with balanced expansion of Th1 and Th2 immunity. Despite elevated levels of cytokines, induction of IL-17A remains minimal.
Article
Immunology
Chi-Ho Lee, Victor Gray, Jia Ming Nickolas Teo, Anthony Raymond Tam, Carol Ho-Yi Fong, David Tak-Wai Lui, Polly Pang, Kwok Hung Chan, Ivan Fan-Ngai Hung, Kathryn Choon-Beng Tan, Guang Sheng Ling
Summary: This study evaluated the impact of type 2 diabetes (T2D) on the immunological responses induced by two COVID-19 vaccines, mRNA (BNT162b2) and inactivated (CoronaVac). The results showed that T2D impaired immune responses induced by CoronaVac, while the initial defect in CD4(+)T cells induced by BNT162b2 was rectified by the second dose. The findings provide a potential mechanism for the susceptibility of COVID-19 patients with T2D to adverse outcomes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell & Tissue Engineering
WonKyung J. Cho, Sharad K. Mittal, Sunil K. Chauhan
Summary: Mounting evidence has shown that mesenchymal stromal cells (MSCs) can suppress CD4(+) T-cell activation, but the exact role of MSCs in regulating the activation and expansion of allogeneic T cells is still unclear. In this study, we found that both human and murine MSCs express ALCAM, a ligand for CD6 receptors on T cells, and investigated its immunomodulatory function using experiments in vivo and in vitro. Our results demonstrated that the ALCAM-CD6 pathway plays a critical role in MSCs' suppressive function on early CD4(+)CD25(-) T-cell activation. Moreover, blocking ALCAM or CD6 abolished the MSC-mediated suppression of T-cell expansion. In a mouse model, MSCs with silenced ALCAM failed to suppress the generation of alloreactive IFN gamma-secreting T cells, leading to allosensitization and alloreactive T-cell-mediated tissue damage.
STEM CELLS TRANSLATIONAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
O. Hecmarie Melendez-Fernandez, James C. Walton, A. Courtney DeVries, Randy J. Nelson
Summary: Cardiovascular diseases are a leading cause of mortality globally, with modifiable risk factors playing a crucial role in addressing these conditions. However, environmental factors disrupting physiological rhythms may increase the risk of cardiovascular diseases and have significant effects on mammalian physiology and behavior.
Review
Immunology
William H. Walker, Jacob R. Bumgarner, Darius D. Becker-Krail, Laura E. May, Jennifer A. Liu, Randy J. Nelson
Summary: The problem of artificial light at night is becoming increasingly serious, affecting people's circadian rhythms and immune function, and also having negative impacts on the environment. With the progress of urbanization and the widespread use of smart devices, the harmful effects of artificial light at night are growing.
SEMINARS IN IMMUNOPATHOLOGY
(2022)
Article
Pharmacology & Pharmacy
Aejin Lee, McKensie L. Mason, Tao Lin, Shashi Bhushan Kumar, Devan Kowdley, Jacob H. Leung, Danah Muhanna, Yuan Sun, Joana Ortega-Anaya, Lianbo Yu, Julie Fitzgerald, A. Courtney DeVries, Randy J. Nelson, Zachary M. Weil, Rafael Jimenez-Flores, Jon R. Parquette, Ouliana Ziouzenkova
Summary: This study compares the effects of free insulin to insulin bound to AACs nanofibers in type 1 diabetes models. The results show that the AAC2-hINS complex significantly improves glucose levels, insulin levels, and neurotransmitter expression, and enhances physical and cognitive performance.
Article
Biology
Randy J. Nelson, Jacob R. Bumgarner, Jennifer A. Liu, Jharnae A. Love, O. Hecmarie Melendez-Fernandez, Darius D. Becker-Krail, William H. Walker, James C. Walton, A. Courtney DeVries, Brian J. Prendergast
Summary: Circadian rhythms are important for biology, but often ignored in research design and reporting. This study analyzed the top-cited papers in 2015 and 2019 and found that most papers lacked sufficient temporal details. There were no significant differences in time-of-day reporting between the two years.
Article
Behavioral Sciences
Robin Oliverio, Julie Fitzgerald, Ruth Velazquez-Cruz, Bailey Whitehead, Kate Karelina, Zachary M. Weil
Summary: This study found that perinatal androgen administration and adult ovariectomy could prevent the development of conditioned place preference to ethanol in female mice after injury. Additionally, gonadectomy did not affect the severity of axonal degeneration, and while TBI increased the number of microglia in males, gonadectomy did not have a corresponding effect.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2022)
Article
Neurosciences
Zachary M. Weil, Brishti White, Bailey Whitehead, Kate Karelina
Summary: Traumatic brain injury (TBI) is a significant public health concern, with a subset of patients experiencing prolonged and severe symptoms. Exaggerated physiological and psychological stress responses after TBI can hinder functional recovery. This article discusses the impact of stress physiology and allostatic loading, as studied by Dr. Bruce McEwen, on TBI patients both before and after their injuries. It explores the role of the hypothalamic-pituitary-adrenal axis responses in TBI and recovery, as well as the effects of stressors and stress responses in promoting post-concussive syndrome and post-traumatic stress disorders. Early life stressors are also considered as modulators of injury outcomes.
NEUROBIOLOGY OF STRESS
(2022)
Article
Biology
Jennifer A. Liu, James C. Walton, Jacob R. Bumgarner, William H. Walker, O. Hecmarie Melendez-Fernandez, A. Courtney DeVries, Randy J. Nelson
Summary: Chronic exposure to artificial light at night (ALAN) affects immune response and lifespan in aged female mice, while it has no significant impact on male mice.
CHRONOBIOLOGY INTERNATIONAL
(2022)
Article
Critical Care Medicine
Bailey Whitehead, Ruth Velazquez-Cruz, Ali Albowaidey, Ning Zhang, Kate Karelina, Zachary M. Weil
Summary: Mild traumatic brain injury (mTBI) leads to persistent cerebrovascular impairments and increased susceptibility to ischemic stroke. The mechanisms behind these effects differ between males and females.
JOURNAL OF NEUROTRAUMA
(2023)
Review
Critical Care Medicine
Zachary M. M. Weil, Julia T. T. Ivey, Kate Karelina
Summary: Rest after traumatic brain injury has a long history and is still recommended, although the rationale was not historically grounded in theory or empirical data. The definition and parameters of rest have evolved over time, including recommendations to avoid various stimuli and cognitive effort. The modern conception of rest aims at preventing reinjury and reducing metabolic demands on injured tissue.
JOURNAL OF NEUROTRAUMA
(2023)
Review
Biochemistry & Molecular Biology
O. Hecmarie Melendez-Fernandez, Jennifer A. Liu, Randy J. Nelson
Summary: Availability of artificial light and light-emitting devices have changed human temporal life, but exposure to artificial light at night disrupts circadian rhythms and increases the risk of metabolic and cardiac disorders. Circadian rhythms, regulated by the suprachiasmatic nucleus (SCN), control physiological processes such as sleep and food intake. Modern lighting disrupts the molecular clock rhythms, leading to hormonal and metabolic disruptions. Understanding these disruptions and developing strategies to mitigate their effects is crucial for human health.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Brishti A. White, Julia T. Ivey, Ruth Velazquez-Cruz, Robin Oliverio, Bailey Whitehead, Mark Pinti, John Hollander, Li Ma, Gangquin Hu, Zachary M. Weil, Kate Karelina
Summary: Physical exercise is a potentially beneficial rehabilitation approach for traumatic brain injury (TBI) recovery. This study examined the effects of post-injury exercise on cognitive function, histopathology, mitochondrial function, and oxidative stress in male and female mice with controlled cortical impact (CCI) injury. The results showed that exercise had different effects on cognitive recovery and mitochondrial function depending on the intensity and sex of the mice, indicating the importance of individualized rehabilitation strategies for TBI patients.
EXPERIMENTAL NEUROLOGY
(2023)
Review
Neurosciences
Bailey Whitehead, Kate Karelina, Zachary M. Weil
Summary: Pericytes play a critical role in the neurovascular unit but are understudied. Dysfunction of pericytes can contribute to deleterious vascular consequences of ischemic stroke. There are limited therapeutic options targeting pericyte function, and further research is needed.
JOURNAL OF NEUROSCIENCE RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Claire O. Kisamore, Brittany D. Elliott, A. Courtney Devries, Randy J. Nelson, William H. Walker II
Summary: Circadian rhythms are internal manifestations of the 24-h solar day that synchronize biological and behavioral processes to improve adaptive function and survival. Chronotherapy optimizes drug administration based on circadian rhythms to achieve maximum therapeutic efficacy and minimize side effects. This review examines the evidence for chronotherapeutic treatment for solid tumors, including chrono-chemotherapy, chrono-radiotherapy, and alternative chronotherapeutics, and discusses areas for further research and challenges in the field.
Editorial Material
Biochemistry & Molecular Biology
James C. Walton, Randy J. Nelson