Article
Cell Biology
Sjoerd van der Post, George M. H. Birchenough, Jason M. Held
Summary: The proliferation of colonic stem cells (CSCs) is mediated by redox-dependent activation of epidermal growth factor receptor (EGFR) signaling via NADPH oxidase 1 (NOX1). NOX1 expression is CSC-specific and regulated by Toll-like receptor activation in response to the microbiota, linking CSC proliferation with the presence of bacterial components in the crypt.
Article
Chemistry, Physical
Geraldine M. Jowett, Michael D. A. Norman, Tracy T. L. Yu, Patricia Rosell Arevalo, Dominique Hoogland, Suzette T. Lust, Emily Read, Eva Hamrud, Nick J. Walters, Umar Niazi, Matthew Wai Heng Chung, Daniele Marciano, Omer S. Omer, Tomasz Zabinski, Davide Danovi, Graham M. Lord, Jons Hilborn, Nicholas D. Evans, Cecile A. Dreiss, Laurent Bozec, Oommen P. Oommen, Christian D. Lorenz, Ricardo M. P. da Silva, Joana F. Neves, Eileen Gentleman
Summary: Type-1 innate lymphoid cells drive intestinal epithelial proliferation and extracellular matrix remodelling through TGF-beta 1 secretion, which could exacerbate inflammatory bowel disease comorbidities such as cancer and fibrosis.
Article
Cell Biology
Riccardo Guidi, Daqi Xu, David F. Choy, Thirumalai R. Ramalingam, Wyne P. Lee, Zora Modrusan, Yuxin Liang, Scot Marsters, Avi Ashkenazi, Alison Huynh, Jessica Mills, Sean Flanagan, Shannon Hambro, Victor Nunez, Laurie Leong, Ashley Cook, Tiffany Hao Tran, Cary D. Austin, Yi Cao, Christine Clarke, Reynold A. Panettieri, Cynthia Koziol-White, William F. Jester, Fen Wang, Mark S. Wilson
Summary: Asthma and inflammatory airway diseases restrict lung airflow and function. Inhaled corticosteroids (ICSs) can reduce inflammation and improve symptoms, but some severe asthma patients do not benefit from ICS. This study identified a corticosteroid-driven fibroblast growth factor (FGF)-dependent inflammatory axis and found that combination therapy with pan-FGF receptor inhibitors and corticosteroids can prevent both eosinophilic and steroid-induced neutrophilic inflammation.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Juan Camilo Castrillon-Betancur, Victor Alonso Lopez-Agudelo, Nina Sommer, Sven Cleeves, Joana Pimenta Bernardes, Saskia Weber-Stiehl, Philip Rosenstiel, Felix Sommer
Summary: This study reveals the bidirectional interaction between DUOX2 and the gut microbiome in contributing to mucosal homeostasis, and their dysregulation may drive disease development. This highlights the potential of targeting the DUOX2-microbiome axis as a therapeutic approach for treating intestinal inflammation.
Article
Oncology
Julia L. Drewes, Jie Chen, Nicholas O. Markham, Reece J. Knippel, Jada C. Domingue, Ada J. Tam, June L. Chan, Lana Kim, Madison McMann, Courtney Stevens, Christine M. Dejea, Sarah Tomkovich, John Michel, James R. White, Fuad Mohammad, Victoria L. Campodonico, Cody N. Heiser, Xinqun Wu, Shaoguang Wu, Hua Ding, Patricia Simner, Karen Carroll, Martha J. Shrubsole, Robert A. Anders, Seth T. Walk, Christian Jobin, Fengyi Wan, Robert J. Coffey, Franck Housseau, Ken S. Lau, Cynthia L. Sears
Summary: This study reveals the role of toxigenic Clostridioides difficile in promoting colorectal cancer, suggesting that chronic colonization with this pathogenic bacteria may drive tumor development through the induction of Wnt signaling, reactive oxygen species, and protumorigenic mucosal immune responses.
Article
Immunology
Niina Bhattarai, Maria Hytti, Mika Reinisalo, Kai Kaarniranta, Yashavanthi Mysore, Anu Kauppinen
Summary: In addition to hypoxia, inflammation can also induce the expression of vascular endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells. Excessive VEGF promotes choroidal neovascularization, contributing to the pathogenesis of wet age-related macular degeneration (AMD). However, excessive dampening of VEGF can lead to RPE degeneration. This study found that hydroquinone, a component of tobacco smoke and a major environmental risk factor for AMD, reduces VEGF levels in inflammatory conditions and may predispose to dry AMD.
IMMUNOLOGIC RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Brittany Woodby, Erika Pambianchi, Francesca Ferrara, Jean-Philippe Therrien, Alessandra Pecorelli, Nicolo' Messano, Mary Ann Lila, Giuseppe Valacchi
Summary: Exposure to O3 is reported to affect AMP levels in the skin, playing a role in skin inflammatory conditions, indicating a possible defensive strategy against pollution-associated skin conditions.
Article
Immunology
Isabelle Mueller, Urs Kym, Virginie Galati, Sasha Tharakan, Ulrike Subotic, Thomas Krebs, Eleuthere Stathopoulos, Peter Schmittenbecher, Dietmar Cholewa, Philipp Romero, Bertram Reingruber, Stefan Holland-Cunz, Simone Keck
Summary: Infants affected by Hirschsprung disease lack ganglia in a variable length of the colon and are prone to developing severe Hirschsprung-associated enterocolitis. Cholinergic signaling has been found to reduce inflammatory response, and the lack of cholinergic innervation correlates with higher incidence of enterocolitis. Cholinergic signals suppress the secretion of IL-8, a pro-inflammatory cytokine, in intestinal epithelial cells via the alpha 7 nicotinic acetylcholine receptor.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Thorsten Joeris, Cristina Gomez-Casado, Petra Holmkvist, Simon J. Tavernier, Aaron Silva-Sanchez, Luisa Klotz, Troy D. Randall, Allan M. Mowat, Knut Kotarsky, Bernard Malissen, William W. Agace
Summary: The study revealed that peripheral cross-tolerance to intestinal epithelial cell (IEC)-derived antigen involves the generation and suppressive function of FoxP3(+)CD8(+) T cells, which requires the involvement of intestinal cDC1. Factors such as PD-L1, TGF beta, and retinoic acid contribute to the generation of gut-tropic CCR9(+)CD103(+)FoxP3(+)CD8(+) T-regs. CD103 deficiency in CD8(+) T cells results in a lack of tolerogenic activity in vivo.
SCIENCE IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Juan A. De la Cruz, Thota Ganesh, Becky A. Diebold, Weiping Cao, Amelia Hofstetter, Neetu Singh, Amrita Kumar, James McCoy, Priya Ranjan, Susan M. E. Smith, Suryaprakash Sambhara, J. David Lambeth, Shivaprakash Gangappa
Summary: TG6-44 can significantly reduce ROS and inflammatory mediators induced by influenza A virus infection, demonstrate antiviral effects in cells, and lead to decreased virus-induced cell death.
Article
Toxicology
R. Begum, S. Thota, S. Batra
Summary: Exposure to cigarettes and e-cigarettes can cause persistent inflammation in the lung, leading to respiratory diseases. Our study demonstrates that LMP7, a proteasome subunit, plays a crucial role in regulating the inflammatory response induced by e-cigarette vapor.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Nutrition & Dietetics
Balaji Venkataraman, Saeeda Almarzooqi, Vishnu Raj, Abdullah T. Alhassani, Ahmad S. Alhassani, Khadijah J. Ahmed, Veedamali S. Subramanian, Shreesh K. Ojha, Samir Attoub, Thomas E. Adrian, Sandeep B. Subramanya
Summary: The study found that thymoquinone (TQ) has anti-inflammatory effects on colonic inflammation, reducing disease activity index and inflammatory mediator expression. TQ can induce potent anti-inflammatory activity by regulating signal pathways and transcription factor expression.
Article
Medicine, Research & Experimental
Janis Kerkering, Bakhrom Muinjonov, Kamil S. Rosiewicz, Sebastian Diecke, Charlotte Biese, Juliane Schiweck, Claudia Chien, Dario Zocholl, Thomas Conrad, Friedemann Paul, Marlen Alisch, Volker Siffrin
Summary: Multiple sclerosis (MS) is a common chronic central nervous system inflammatory disease with variable clinical courses. Researchers investigated the mechanisms in benign MS (BMS) compared with progressive MS (PMS) using induced pluripotent stem cells (iPSCs). They found that BMS astrocytes exhibited less axonal damage and upregulated neuronal resilience pathways, accompanied by differential growth factor expression. Furthermore, cocultures of BMS astrocytes and neurons showed neuroprotective effects against inflammatory-induced neurite damage through the expression of specific growth factors and JAK-STAT activation.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Oncology
Takayasu Ideta, Boyang Li, Christopher Flynn, Yuichi Igarashi, Geoffrey Lowman, Tim Looney, Thomas J. Devers, John Birk, Faripour Forouhar, Charles Giardina, Daniel W. Rosenberg
Summary: Stromal cells are crucial in promoting colorectal cancer progression, with involvement in localized inflammation, reduced interferon signaling and cell-based immunity. The upregulation of immune checkpoint and T-cell exhaustion gene PDCD1, accompanied by decreased expression of cytotoxic T-cell effector genes, is observed. CDKN2A expression is strongly upregulated in the stroma and downregulated in the epithelium, indicating diverse changes in senescence-associated signaling between these tissue compartments.
MOLECULAR CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Pang-Yen Tseng, Mark A. Hoon
Summary: This study identifies GPR15L as a candidate pruritogen that is up-regulated in psoriasis and atopic dermatitis. The researchers also show that GPR15L activates Mas-related G protein-coupled receptors (MRGPRs) and contributes to itch responses by stimulating mouse dorsal root ganglion neurons. Furthermore, they demonstrate that GPR15L causes mast cell degranulation. Genetic disruption of GPR15L reduces scratch responses in a mouse model of psoriasis.
Article
Immunology
Sarah M. Wade, Michelle Trenkmann, Trudy McGarry, Mary Canavan, Viviana Marzaioli, Siobhan C. Wade, Douglas J. Veale, Ursula Fearon
JOURNAL OF AUTOIMMUNITY
(2019)
Article
Immunology
Delphine Ohayon, Alessia De Chiara, Pham My-Chan Dang, Nathalie Thieblemont, Simon Chatfield, Viviana Marzaioli, Sabrina Sofia Burgener, Julie Mocek, Celine Candalh, Coralie Pintard, Pascale Tacnet-Delorme, Gilles Renault, Isabelle Lagoutte, Maryline Favier, Francine Walker, Margarita Hurtado-Nedelec, Dominique Desplancq, Etienne Weiss, Charaf Benarafa, Dominique Housset, Jean-Claude Marie, Philippe Frachet, Jamel El-Benna, Veronique Witko-Sarsat
JOURNAL OF EXPERIMENTAL MEDICINE
(2019)
Article
Immunology
M. Canavan, V. Marzaioli, T. McGarry, V. Bhargava, S. Nagpal, D. J. Veale, U. Fearon
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2020)
Article
Immunology
Viviana Marzaioli, Mary Canavan, Achilleas Floudas, Siobhan C. Wade, Candice Low, Douglas J. Veale, Ursula Fearon
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Immunology
Trudy McGarry, Megan M. Hanlon, Viviana Marzaioli, Clare C. Cunningham, Vinod Krishna, Kieran Murray, Conor Hurson, Phil Gallagher, Sunil Nagpal, Douglas J. Veale, Ursula Fearon
Summary: This study reveals that monocytes in RA patients exhibit hyper-inflammatory responses and metabolic reprogramming, with evidence of this phenotype appearing before clinical manifestations of the disease.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2021)
Article
Immunology
Aisling O'Brien, Megan Mary Hanlon, Viviana Marzaioli, Siobhan C. Wade, Keelin Flynn, Ursula Fearon, Douglas J. Veale
Summary: The study demonstrates the crucial role of JAK/STAT signaling in the pathogenesis of PsA, with JAKi effectively suppressing inflammatory mechanisms and supporting their role as a therapeutic target for PsA treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Viviana Marzaioli, Mary Canavan, Achilleas Floudas, Keelin Flynn, Ronan Mullan, Douglas J. Veale, Ursula Fearon
Summary: Dendritic cells (DC) play a crucial role in the development of inflammatory arthritis. A unique population of DC derived from monocytes, called CD209/CD14(+) DC, was identified in the blood of healthy individuals as well as patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). These CD209/CD14(+) DC exhibited distinct characteristics and increased expression of inflammatory cytokines in the circulation of patients. Furthermore, they displayed a unique inflammatory and maturation phenotype in the inflamed joint. A novel protocol for isolating and expanding CD209(+) DC was developed, revealing transcriptional differences between RA and PsA CD209(+) DC. Additionally, culture of healthy CD209(+) DC with synovial fluid from patients with IA induced the development of CD209/CD14(+) DC, accompanied by changes in chemokine receptor and chemokine expression. The JAK/STAT pathway was found to regulate the function of CD209/CD14(+) DC, suggesting its potential as a therapeutic target for reducing inflammation. Overall, this study provides insights into the role of CD209/CD14(+) DC in IA and highlights the potential of targeting the JAK/STAT pathway for therapeutic intervention.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Mary Canavan, Viviana Marzaioli, Vipul Bhargava, Sunil Nagpal, Phil Gallagher, Conor Hurson, Ronan Mullan, Douglas J. Veale, Ursula Fearon
Summary: In patients with Inflammatory Arthritis, synovial CD1c(+)DCs exhibit distinct transcriptional and maturation signatures compared to peripheral CD1c(+)DCs and synovial CD141(+)DCs, with functional differences in TLR7/8 response, antigen processing, and MMP production.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Sahra Amel Belambri, Viviana Marzaioli, Margarita Hurtado-Nedelec, Coralie Pintard, Shiyu Liang, Yezhou Liu, Tarek Boussetta, Marie-Anne Gougerot-Pocidalo, Richard D. Ye, Pham My-Chan Dang, Jamel El-Benna
Summary: This study discovered that p67phox and p40phox are novel regulators of p47phox phosphorylation at specific sites, which is essential for superoxide production by phagocytes and immune response.
Review
Medicine, General & Internal
Achilleas Floudas, Aine Gorman, Nuno Neto, Michael G. Monaghan, Zoe Elliott, Ursula Fearon, Viviana Marzaioli
Summary: Inflammatory arthritis is a chronic autoimmune disease that affects the joints. Understanding the early events that lead to synovial inflammation is challenging, but the utilization of high-throughput techniques can provide valuable insights. This review summarizes key methods and novel techniques used in the handling, processing, and analysis of synovial tissue biopsies, and discusses the impact of different storage and handling techniques on downstream analysis. Implementation of these new approaches will accelerate our understanding of the mechanisms involved in inflammatory arthritis and lead to the identification of new therapeutic interventions.
FRONTIERS IN MEDICINE
(2022)
Article
Rheumatology
Achilleas Floudas, Conor M. Smith, Orla Tynan, Nuno Neto, Vinod Krishna, Sarah M. Wade, Megan Hanlon, Clare Cunningham, Viviana Marzaioli, Mary Canavan, Jean M. Fletcher, Ronan H. Mullan, Suzanne Cole, Ling-Yang Hao, Michael G. Monaghan, Sunil Nagpal, Douglas J. Veale, Ursula Fearon
Summary: This study provides a global transcriptomic analysis of the synovial joints in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), revealing the immune-stromal cell interactions in synovial inflammation. The findings highlight the differential transcription profiles and interactions between cell subsets in RA and PsA, suggesting potential targets for targeted therapeutic intervention in these diseases.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Rheumatology
Megan M. Hanlon, Trudy McGarry, Viviana Marzaioli, Success Amaechi, Qingxuan Song, Sunil Nagpal, Douglas J. Veale, Ursula Fearon
Summary: This study investigates the metabolic activity of infiltrating polarized macrophages in rheumatoid arthritis (RA) and their impact on pro-inflammatory responses. The researchers found that RA macrophages exhibit a unique inflammatory and metabolic phenotype, characterized by heightened expression of key cytokines and altered mitochondrial morphology. Furthermore, the study identifies NAMPT and STAT3 signaling as key regulators of this phenotype.
Article
Medicine, General & Internal
Brianne E. Barker, Megan M. Hanlon, Viviana Marzaioli, Conor M. Smith, Clare C. Cunningham, Jean M. Fletcher, Douglas J. Veale, Ursula Fearon, Mary Canavan
Summary: This study investigates the role of the mTOR pathway in the metabolism and activation of rheumatoid arthritis synovial fibroblasts (RASF), and identifies crosstalk with the Hippo-YAP pathway. The results suggest that mTOR mediates the invasive mechanism of RASF through the Hippo-YAP pathway.
FRONTIERS IN MEDICINE
(2023)
Meeting Abstract
Rheumatology
Viviana Marzaioli, Mary Canavan, Achilleas Floudas, Keelin Flynn, Ronan Mullan, Douglas Veale, Ursula Fearon
ARTHRITIS & RHEUMATOLOGY
(2021)
Article
Medicine, Research & Experimental
Achilleas Floudas, Nuno Neto, Viviana Marzaioli, Kieran Murray, Barry Moran, Michael G. Monaghan, Candice Low, Ronan H. Mullan, Navin Rao, Vinod Krishna, Sunil Nagpal, Douglas J. Veale, Ursula Fearon