Review
Oncology
Franklin Ning, Christopher B. Cole, Christina M. Annunziata
Summary: Ovarian cancer is a leading cause of death among gynecological neoplasms, with first-line treatment options focusing on taxane and platinum-based chemotherapy. Despite recent advancements in immunotherapy, its effectiveness in ovarian cancer is limited due to the highly immunosuppressive tumor microenvironment. Understanding the interactions among immune cell subsets within the peritoneal microenvironment is crucial for developing efficacious therapies.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Young Jae Kim, Eun-Jin Park, Sang-Hee Lee, Prashanta Silwal, Jin Kyung Kim, Jeong Seong Yang, Jake Whang, Jichan Jang, Jin-Man Kim, Eun-Kyeong Jo
Summary: In this study, dimethyl itaconate (DMI) was found to have potential as a candidate for host-directed therapy (HDT) against both Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria. It can activate multiple immune defense mechanisms in the host to promote intracellular killing of mycobacteria and suppress inflammation. This research contributes to the development of new anti-tuberculosis drugs.
CELL AND BIOSCIENCE
(2023)
Article
Cell Biology
Nivedita Hegdekar, Chinmoy Sarkar, Sabrina Bustos, Rodney M. M. Ritzel, Marie Hanscom, Prarthana Ravishankar, Deepika Philkana, Junfang Wu, David J. J. Loane, Marta M. M. Lipinski
Summary: Excessive and prolonged neuroinflammation following traumatic brain injury (TBI) is associated with inhibited autophagy in neurons, microglia, and infiltrating macrophages. Macrophage/microglia-specific knockout of the essential autophagy gene Becn1 increases neuroinflammation after TBI, which is characterized by excessive activation of innate immune responses. Defects in microglial and macrophage autophagy following injury result in decreased clearance of danger/damage-associated molecular patterns, and inhibition of microglial/macrophage autophagy leads to increased neurodegeneration and worse cognitive outcomes.
Article
Microbiology
Sapna Saini, Anjali Gangwar, Rashmi Sharma
Summary: Tuberculosis (TB) is a highly contagious bacterial infection caused by Mycobacterium tuberculosis (Mtb), and it ranks as the second leading cause of death worldwide from a single infectious agent. Mtb has adapted to the phagocytic host microenvironment, influencing various host processes and attenuating host cellular processes for its survival. Recent research has identified specific host genes and mechanisms involved in the intracellular entry and stabilization of M. tuberculosis, providing new possibilities for host-directed therapeutics (HDT). This review discusses the host-pathogen interaction for Mtb, including the pathways adapted by Mtb to escape immunity, and explores different HDTs such as repurposed drugs and vitamins.
MICROBIOLOGICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Annette Ives, Didier Le Roy, Charlotte Theroude, Juergen Bernhagen, Thierry Roger, Thierry Calandra
Summary: The cytokine MIF plays a chemokine-like role in promoting the migration of dendritic cells (DCs) by activating the Src/PI3K signaling pathway and myosin II complexes. MIF contributes to the recruitment of DCs to draining lymph nodes through autocrine and paracrine activities acting via CD74. These findings indicate that MIF is crucial for DC motility and trafficking.
Article
Entomology
Bo Qin, Shichao Yu, Qiming Chen, Li Hua Jin
Summary: Autophagy is an essential cellular process that regulates development and stress responses. However, its role in innate immunity is not well understood. In this study, we demonstrated that Atg2, an autophagy-related protein, plays an important role in controlling innate immunity in Drosophila melanogaster. Inhibiting Atg2 led to the formation of melanotic nodules, disrupted phagocytosis, altered the expression of AMP-encoding genes, and impaired the ability to resist bacterial infections.
Review
Gastroenterology & Hepatology
Natsuki Okai, Tomohiro Watanabe, Kosuke Minaga, Ken Kamata, Hajime Honjo, Masatoshi Kudo
Summary: Crohn's disease (CD) is caused by the loss of tolerance to intestinal microbiota and excessive production of pro-inflammatory cytokines. Impaired activation of pattern recognition receptor (PRR)-mediated signaling pathways and dysfunction of the autophagic machinery may be involved in the development of CD.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jianwei Mao, Shaotang Ye, Jie Deng, Jie Song, Zhen Wang, Aolei Chen, Pei Zhou, Shoujun Li
Summary: Feline calicivirus (FCV) is a pathogen that can cause severe upper respiratory tract disease in cats. This study discovered that FCV infection triggers autophagy, with non-structural proteins responsible for initiating the process. Modulating autophagy levels had different effects on FCV replication, and increased autophagy suppressed FCV-induced RIG-I signal transduction. These findings provide insights into FCV replication mechanisms and have potential implications for drug development against FCV infection targeting autophagy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Po-Yuan Ke
Summary: Autophagy regulates cellular metabolism and acts as a defense mechanism against viral infections. Recent studies have shown that virus-induced autophagy may promote viral replication by modulating host cellular processes, including the regulation of innate immunity mediated by RLR. This article provides an overview of the functional molecules and regulatory mechanisms of RLR antiviral immune response and autophagy, and summarizes the role of autophagy in regulating RLR antiviral signaling and the crosstalk between autophagy and RLR innate immunity.
Article
Fisheries
Hongyan Yu, Xuewen Jia, Yifan Pang, Huiqin Niu, Biao Du, Xiaoyan Xu, Jiale Li
Summary: In this study, it was found that the TBK1 gene in grass carp could be upregulated by bacterial infection. Overexpression of TBK1 could reduce the number of adhesive bacteria in cells and promote cellular migration, proliferation, vitality, and anti-apoptosis ability. TBK1 could activate the NF-kappa B signaling pathway and induce autophagy in cells. These findings provide important information about the defense and immune mechanisms used by grass carp against pathogens.
FISH & SHELLFISH IMMUNOLOGY
(2023)
Article
Fisheries
Jiaqian Zhu, Yina Shao, Kaiyu Chen, Weiwei Zhang, Chenghua Li
Summary: Transglutaminases (TGases) play critical roles in innate immunity, with TGase2 involved in autophagy to help degrade protein aggregates. A novel TGase2-like gene, AjTGase2-like, was cloned from the sea cucumber Apostichopus japonicus, showing high conservation with vertebrate TGase2. AjTGase2-like was widely expressed and played a key role in immune response, acting as a positive regulator in sea cucumber autophagy.
FISH & SHELLFISH IMMUNOLOGY
(2021)
Article
Cell Biology
Mario A. Lauterbach, Victor Saavedra, Matthew S. J. Mangan, Anke Penno, Christoph Thiele, Eicke Latz, Lars Kuerschner
Summary: The study reveals that deoxysphingolipids have an impact on autophagy, potentially leading to inflammation and abnormalities in the innate immune system.
Article
Microbiology
Anna K. P. Serquina, Takanobu Tagawa, Daniel Oh, Guruswamy Mahesh, Joseph M. Ziegelbauer
Summary: 25-hydroxycholesterol (25HC) inhibits infections of Kaposi's sarcoma herpesvirus and Epstein-Barr virus by inducing interferon-stimulated genes and inflammatory cytokines, suppressing key viral genes, and inducing apoptosis. Moreover, it can also be antiviral against various viruses through inducing antiviral interferon response.
Review
Immunology
Wen Jie Yeoh, Philippe Krebs
Summary: The review summarizes the current knowledge of the phosphoinositide phosphatase SHIP1 and its role in regulating innate immune cells. It also discusses the development of small-molecule agonists and antagonists targeting SHIP1, and explores the potential use of SHIP1 modulation in immune therapies for human diseases with unmet medical needs.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Review
Immunology
Prashanta Silwal, In Soo Kim, Eun-Kyeong Jo
Summary: Autophagy plays a crucial role in enhancing the immune responses and controlling inflammation against NTM infections, and holds potential as a therapeutic target for combating NTM infections.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Rheumatology
Yoshiya Tanaka, Tatsuya Atsumi, Masato Okada, Tomoya Miyamura, Tomonori Ishii, Susumu Nishiyama, Ryutaro Matsumura, Nobuya Hayashi, Gabriel Abreu, Raj Tummala, Eric F. Morand, Tsutomu Takeuchi
Summary: This study evaluated the efficacy and safety of anifrolumab in Japanese patients with SLE. The results showed that anifrolumab was more effective than placebo in improving patients' condition and reducing skin activity. In terms of safety, anifrolumab had a profile consistent with the overall population.
MODERN RHEUMATOLOGY
(2023)
Article
Rheumatology
Sayuri Yamashita, Yasuhiro Katsumata, Naoko Konda, Rangi Kandane-Rathnayake, Eric F. Morand, Masayoshi Harigai
Summary: This study compared the US norm-based two-component and Japanese norm-based three-component models of the Medical Outcomes Study Short Form-36 (SF-36) in patients with systemic lupus erythematosus (SLE). The results showed that although the agreement between the two models was insufficient, their scores demonstrated similar associations with other variables.
MODERN RHEUMATOLOGY
(2023)
Article
Rheumatology
Ai Li Yeo, Michelle Leech, Samar Ojaimi, Eric Morand
Summary: The utility of repeat ENA testing after an initial negative result was assessed in this study. A retrospective study was conducted in a single, multicentre tertiary health network in Melbourne, Australia. The results showed that repeat ENA test results rarely change or result in a new diagnosis of an ANA-associated rheumatic disease (AARD), with repeated testing only warranted if there is a change in clinical manifestations.
Article
Rheumatology
Ai Li Yeo, Samar Ojaimi, Suong Le, Michelle Leech, Eric Morand
Summary: Simultaneous antibody testing during screening for autoimmune conditions is not recommended. This study aimed to investigate the frequency of new diagnosis of ANA-associated rheumatic disease (AARD) in patients with negative ANA but positive ENA. Results showed a low yield of newly diagnosed rheumatic diseases, despite the higher-than-expected incidence of positive ENA in the setting of a negative ANA. These findings support the stepwise addition of ENA requests when ANA test result is positive and clinical suspicion of AARD is high.
ARTHRITIS CARE & RESEARCH
(2023)
Article
Rheumatology
Ian N. Bruce, Ronald F. van Vollenhoven, Eric F. Morand, Richard A. Furie, Susan Manzi, William B. White, Gabriel Abreu, Raj Tummala
Summary: This study evaluated the effects of sustained glucocorticoid tapering in patients with SLE. The results showed that sustained glucocorticoid tapering is associated with reduced glucocorticoid dosage, improved patient-reported outcomes, and fewer adverse events. Treatment with anifrolumab has the potential to reduce disease activity and glucocorticoid exposure.
Article
Rheumatology
Eric F. Morand, Gabriel Abreu, Richard A. Furie, Vera Golder, Raj Tummala
Summary: A post hoc analysis reveals that treatment with anifrolumab in patients with SLE leads to earlier, more frequent, and more sustained attainment of LLDAS. LLDAS is highly associated with responses measured by BICLA and SRI(4).
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Respiratory System
Venkata Sita Rama Raju Allam, Stelios Pavlidis, Gang Liu, Nazanin Zounemat Kermani, Jennifer Simpson, Joyce To, Sheila Donnelly, Yi-Ke Guo, Philip M. Hansbro, Simon Phipps, Eric F. Morand, Ratko Djukanovic, Peter Sterk, Kian Fan Chung, Ian Adcock, James Harris, Maria B. Sukkar
Summary: The study showed that MIF protein correlates with clinical and molecular features of severe neutrophilic asthma and reduces the biological activity of annexin-A1 through interaction, promoting glucocorticoid resistance of neutrophilic inflammation.
Article
Rheumatology
Kenneth C. Kalunian, Richard Furie, Eric F. Morand, Ian N. Bruce, Susan Manzi, Yoshiya Tanaka, Kevin Winthrop, Ihor Hupka, Lijin Jinny Zhang, Shanti Werther, Gabriel Abreu, Micki Hultquist, Raj Tummala, Catharina Lindholm, Hussein Al-Mossawi
Summary: This study investigates the long-term safety and tolerability of anifrolumab 300 mg compared with placebo in patients with systemic lupus erythematosus (SLE). The results show that anifrolumab is well-tolerated and has a favorable benefit-risk profile in patients with moderate-to-severe SLE receiving standard therapy.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Rheumatology
Eric Morand, Marilyn Pike, Joan T. Merrill, Ronald van Vollenhoven, Victoria P. Werth, Coburn Hobar, Nikolay Delev, Vaishali Shah, Brian Sharkey, Thomas Wegman, Ian Catlett, Subhashis Banerjee, Shalabh Singhal
Summary: Deucravacitinib treatment showed higher response rates for SRI-4 and other endpoints compared to placebo, with an acceptable safety profile, in adult patients with active SLE.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Rheumatology
Sudha Raghunath, Yifat Glikmann-Johnston, Vera Golder, Rangi Kandane-Rathnayake, Eric F. Morand, Julie C. Stout, Alberta Hoi
Summary: Cognitive dysfunction in SLE is associated with organ damage, but not disease activity, and is negatively associated with serological activity and high IFN signature. Clinicians often fail to recognize cognitive dysfunction in SLE patients.
LUPUS SCIENCE & MEDICINE
(2023)
Article
Rheumatology
Joy Buie, Lauren Bloch, Eric F. Morand, Ronald F. van Vollenhoven, Victoria P. Werth, Zahi Touma, Peter Lipsky, Kenneth Kalunian, Anca D. Askanase, L. Ines, Christopher Reed, MaryBeth Son, Timothy Franson, Karen Costenbader, Laura Eve Schanberg
Summary: Drug development in lupus has improved but lags behind other rheumatic diseases. Challenges in assessing lupus therapies include disease heterogeneity, study design limitations, and lack of validated biomarkers impacting regulatory decision-making. The meeting report addresses the need for standardized outcome measures to accelerate lupus therapeutics development and highlights ongoing efforts in outcome measure development.
LUPUS SCIENCE & MEDICINE
(2023)
Review
Cell Biology
Katie Treasure, James Harris, Gary Williamson
Summary: Dysregulation of innate immune responses can lead to chronic inflammatory conditions. Glucocorticoids are effective but come with serious side effects. Sulforaphane, derived from plants of the brassica family, has shown potential as an alternative therapy due to its induction of detoxification enzymes and anti-inflammatory properties. It may also have steroid-sparing activity, making it a promising adjunctive treatment. Further research is needed to fully understand its clinical applications.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Rheumatology
Eric Morand, Josef S. Smolen, Michelle Petri, Yoshiya Tanaka, Maria Silk, Christina Dickson, Gabriella Meszaros, Inmaculada de la Torre, Maher Issa, Hong Zhang, Thomas Doerner
Summary: This study aimed to assess the safety of the oral Janus kinase inhibitor baricitinib in adult patients with systemic lupus erythematosus (SLE) receiving stable background therapy. The results showed that the infection rate was slightly higher in the baricitinib treatment group compared to the placebo group, but there were no significant adverse events. The incidence of venous thromboembolism was low.
Article
Rheumatology
Matthew Studham, Cristina Vazquez-Mateo, Eileen Samy, Philipp Haselmayer, Aida Aydemir, P. Alexander Rolfe, Joan T. Merrill, Eric F. Morand, Julie Demartino, Amy Kao, Robert Townsend
Summary: This study aims to identify SLE patients most likely to respond to atacicept in the APRIL-SLE and ADDRESS II trials using cell-based gene signatures. An immune cell deconvolution algorithm was applied to analyze gene expression data and five distinct patient clusters were identified. The study also developed a modified immune cell deconvolution algorithm based on RNA sequencing data to identify similar patient clusters and their responses in the ADDRESS II trial.
ACR OPEN RHEUMATOLOGY
(2023)
