Review
Dentistry, Oral Surgery & Medicine
George Hajishengallis, Xiaofei Li, Kimon Divaris, Triantafyllos Chavakis
Summary: This article reviews the bidirectional association between periodontitis and systemic inflammatory disorders. It introduces two newly emerged concepts, trained innate immunity (TII) and clonal hematopoiesis of indeterminate potential (CHIP), which together support a potential hypothesis on how periodontitis affects and is affected by comorbidities and why the susceptibility to periodontitis and comorbidities increases with aging. The article discusses the role of TII and CHIP in mediating the relationship between periodontitis and comorbidities, and proposes that a mechanistic understanding of this connection may lead to novel diagnostic and therapeutic targets for inflammatory comorbidities.
PERIODONTOLOGY 2000
(2022)
Article
Cell Biology
Stefan Kuhnert, Siavash Mansouri, Michael A. Rieger, Rajkumar Savai, Edibe Avci, Gabriela Diaz-Pina, Manju Padmasekar, Mario Looso, Stefan Hadzic, Till Acker, Stephan Klatt, Jochen Wilhelm, Ingrid Fleming, Natascha Sommer, Norbert Weissmann, Claus Vogelmeier, Robert Bals, Andreas Zeiher, Stefanie Dimmeler, Werner Seeger, Soni S. Pullamsetti
Summary: This study found an increased incidence of CHIP mutations in COPD patients, which are associated with hypomethylation of PLD5, leading to elevated levels of glycerol phosphocholine, pro-inflammatory cytokines, and deteriorating lung function.
Article
Hematology
Cedric Pastoret, Fabienne Desmots, Gaelle Drillet, Simon Le Gallou, Marie-Laure Boulland, Alexia Thannberger, Anne-Violaine Doncker, Veronique Salaun, Gandhi Laurent Damaj, Richard Veyrat-Masson, Olivier Tournilhac, Aline Moignet, Celine Pangault, Mikael Roussel, Thierry Fest, Thierry Lamy
Summary: The study provides new insights into the diagnosis and treatment of NK cell proliferative disorders, identifying potential new diagnostic markers to distinguish between CLPD-NK and reactive NK-cell expansion. Furthermore, the discovery of TET2 gene mutations and transcriptome analysis offer valuable information for further research.
Review
Hematology
Robin P. Choudhury, Laurienne Edgar, Mikael Ryden, Edward A. Fisher
Summary: Physiological functions are intricately intertwined, with evidence from immunometabolism field showing that cells can be programmed by changes in metabolic environment through epigenetic modifications, causing persistent changes. Understanding these processes can have significant implications for the diagnosis and treatment of diabetes and related metabolic states.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Niels P. P. Riksen, Siroon Bekkering, Willem J. M. Mulder, Mihai G. G. Netea
Summary: Trained immunity is a mechanism of chronic inflammation in atherosclerotic cardiovascular disease, induced by endogenous factors and lifestyle factors, leading to metabolic and epigenetic reprogramming of myeloid cells. This review discusses the molecular and cellular mechanisms of trained immunity, its activation by cardiovascular risk factors, and potential therapeutic strategies for managing atherosclerotic cardiovascular disease.
NATURE REVIEWS CARDIOLOGY
(2023)
Article
Clinical Neurology
Ernst Mayerhofer, Christoph Strecker, Heiko Becker, Marios K. Georgakis, Md Mesbah Uddin, Michael M. Hoffmann, Niroshan Nadarajah, Manja Meggendorfer, Torsten Haferlach, Jonathan Rosand, Pradeep Natarajan, Christopher D. Anderson, Andreas Harloff, Gregor Hoermann
Summary: Genetic screening in young stroke patients revealed a 3-fold higher prevalence of clonal hematopoiesis compared to the general population. About 4.4% of patients had high-risk clonal hematopoiesis and 1% had covert myeloproliferative neoplasms, requiring specific treatment. These findings highlight the diagnostic and therapeutic value of genetic screening in young stroke patients.
Review
Immunology
Samanta C. Funes, Mariana Rios, Ayleen Fernandez-Fierro, Maria S. Di Genaro, Alexis M. Kalergis
Summary: A dysregulated immune response is a characteristic of autoimmune and autoinflammatory disorders. Monocytes and macrophages (Mo/Ma) have been found to significantly contribute to the development of both types of diseases, but their functional plasticity makes it difficult to understand their exact role.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Public, Environmental & Occupational Health
Min Joo Kim, Han Song, Youngil Koh, Heesun Lee, Hyo Eun Park, Sung Hee Choi, Ji Won Yoon, Su-Yeon Choi
Summary: This study investigated the association between clonal hematopoiesis of indeterminate potential (CHIP) and new-onset type 2 diabetes. The results showed that the incidence of new-onset diabetes was significantly higher in CHIP carriers, especially in those with high LDL cholesterol levels.
FRONTIERS IN PUBLIC HEALTH
(2023)
Article
Cell Biology
Daniel Nachun, Ake T. Lu, Alexander G. Bick, Pradeep Natarajan, Joshua Weinstock, Mindy D. Szeto, Sekar Kathiresan, Goncalo Abecasis, Kent D. Taylor, Xiuqing Guo, Russ Tracy, Peter Durda, Yongmei Liu, Craig Johnson, Stephen S. Rich, David van den Berg, Cecilia Laurie, Tom Blackwell, George J. Papanicolaou, Adolfo Correa, Laura M. Raffield, Andrew D. Johnson, Joanne Murabito, JoAnn E. Manson, Pinkal Desai, Charles Kooperberg, Themistocles L. Assimes, Daniel Levy, Jerome Rotter, Alex P. Reiner, Eric A. Whitsel, James G. Wilson, Steve Horvath, Siddhartha Jaiswal
Summary: Clonal hematopoiesis of indeterminate potential (CHIP) is strongly associated with epigenetic age acceleration, with carriers of multiple gene mutations showing the largest increase in age acceleration. About 40% of CHIP carriers have acceleration >0 in both clocks, and this subgroup is at higher risk for adverse outcomes, making them potential targets for clinical interventions.
Article
Hematology
Thomas L. Olson, HeeJin Cheon, Jeffrey C. Xing, Kristine C. Olson, Umadevi Paila, Cait E. Hamele, Yaseswini Neelamraju, Bryna C. Shemo, Matt Schmachtenberg, Shriram K. Sundararaman, Mariella F. Toro, Cheryl A. Keller, Emily A. Farber, Suna Onengut-Gumuscu, Francine E. Garrett-Bakelman, Ross C. Hardison, David J. Feith, Aakrosh Ratan, Thomas P. Loughran
Summary: Chronic natural killer large granular lymphocyte (NK-LGL) leukemia is a rare disorder characterized by prolonged expansion of clonal NK cells, with unique mutations such as TET2 and STAT3 playing important roles in its pathogenesis.
Article
Cardiac & Cardiovascular Systems
Jesse D. Cochran, Yoshimitsu Yura, Mark C. Thel, Heather Doviak, Ariel H. Polizio, Yuka Arai, Yohei Arai, Keita Horitani, Eunbee Park, Nicholas W. Chavkin, Anupreet Kour, Soichi Sano, Nitin Mahajan, Megan Evans, Mahalia Huba, Nadia Martinez Naya, Hanna Sun, Young Ho Ban, Karen K. Hirschi, Stefano Toldo, Antonio Abbate, Todd E. Druley, Frederick L. Ruberg, Mathew S. Maurer, Justin A. Ezekowitz, Jason R. B. Dyck, Kenneth Walsh
Summary: The study identified an enrichment of TET2-mediated CH in patients with HFpEF, which was associated with exacerbated diastolic dysfunction. Patients with HFpEF, aged >= 70 years and CH, exhibited a worse prognosis in terms of 5-year cardiovascular-related hospitalization rate compared with those without CH.
Article
Multidisciplinary Sciences
Elisa Jentho, Cristian Ruiz-Moreno, Boris Novakovic, Ioannis Kourtzelis, Wout L. Megchelenbrink, Rui Martins, Triantafyllos Chavakis, Miguel P. Soares, Lydia Kalafati, Joel Guerra, Franziska Roestel, Peter Bohm, Maren Godmann, Tatyana Grinenko, Anne Eugster, Martina Beretta, Leo A. B. Joosten, Mihai G. Netea, Michael Bauer, Hendrik G. Stunnenberg, Sebastian Weis
Summary: Trained immunity refers to long-lasting adaptations of innate immunity, and labile heme has been identified as a previously unrecognized inducer of trained immunity. Unlike other inducers that rely on pathogen-associated molecular patterns, heme training activates a unique signaling pathway and is associated with the expansion of self-renewing hematopoetic stem cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Gregoire Martin de Fremont, Pierre Hirsch, Santiago Gimenez de Mestral, Philippe Moguelet, Yoan Ditchi, Jean-Francois Emile, Patricia Senet, Sophie Georgin-Lavialle, Thomas Hanslik, Francois Maurier, Amir Adedjouma, Noemie Abisror, Thibault Mahevas, Florent Malard, Lionel Ades, Pierre Fenaux, Olivier Fain, Francois Chasset, Arsene Mekinian
Summary: In most cases of MDS/CMML, skin lesions are characterized by a clonal myeloid infiltrate, and there is generally a similar mutational profile between blood/bone marrow and skin.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Ahmed A. Z. Dawoud, Rodney D. Gilbert, William J. Tapper, Nicholas C. P. Cross
Summary: The study found an association between age-related clonal hematopoiesis (CH) and chronic kidney disease (CKD), specifically with glomerular filtration rate estimated from cystatin-C (eGFR.cys) as the standard. CH was negatively associated with CKD, particularly in participants without any history of cardiovascular disease or myeloid neoplasms, where clonal hematopoiesis increased the risk of adverse outcomes in CKD.
Article
Urology & Nephrology
Caitlyn Vlasschaert, Amy J. M. McNaughton, Michael Chong, Elina K. Cook, Wilma Hopman, Bryan Kestenbaum, Cassianne Robinson-Cohen, Jocelyn Garland, Sarah M. Moran, Guillaume Pare, Catherine M. Clase, Mila Tang, Adeera Levin, Rachel Holden, Michael J. Rauh, Matthew B. Lanktree
Summary: This study found that genetic mutations in hematopoietic stem cells are associated with the progression of chronic kidney disease and anemia, and individuals with these mutations have a higher risk of kidney failure.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
