Andina, Nicola; de Meuron, Louise; Schnegg-Kaufmann, Annatina Sarah; Ansermet, Camille; Bombaci, Giuseppe; Keller, Nino; Porret, Naomi; Angelillo-Scherrer, Anne; Bonadies, Nicolas; Allam, Ramanjaneyulu (31 January 2022). Heightened NLRP3 inflammasome activation is associated with aging and CMML diseases severity (bioRxiv). Cold Spring Harbor Laboratory 10.1101/2022.01.27.477992
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Aging causes chronic low-grade inflammation known as inflamm-aging. It is a risk factor for
chronic myelomonocytic leukemia (CMML), a hematological malignancy that is most
prevalent in older people. Recent studies suggest a critical role for the NLRP3 inflammasome
in inflamm-aging. However, the mechanisms involved in NLRP3 activation in aging and its
involvement in CMML progression are not fully understood. Here, we report that aging
increases interleukin-1β production upon NLRP3 activation in human CD14+ monocytes.
Interestingly, we found that Toll-like receptor (TLR) 1/2 agonist Pam3Cysk4 directly activates
NLRP3 inflammasome without the requirement of second activation signal in monocytes from
older but not from younger healthy donors. Further, we observed a dichotomous response to
NLRP3 inflammasome activation in monocytes from CMML patients. Intriguingly, CMML
patients with heightened NLRP3 activation showed increased treatment dependency and
disease severity. Collectively, our results suggest that aging causes increased sensitivity to
NLRP3 inflammasome activation at cellular level, which may explain increased inflammation
and immune dysregulation in older individuals. Furthermore, NLRP3 inflammasome activation
was dysregulated in CMML and positively correlated with disease severity.
Item Type: |
Working Paper |
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Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene) |
UniBE Contributor: |
Andina, Nicola, de Meuron, Louise, Schnegg-Kaufmann, Annatina Sara, Ansermet, Camille Eva, Bombaci, Giuseppe, Porret, Naomi, Angelillo, Anne, Bonadies, Nicolas, Allam, Ramanjaneyulu |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2692-8205 |
Series: |
bioRxiv |
Publisher: |
Cold Spring Harbor Laboratory |
Language: |
English |
Submitter: |
Pierrette Durand Lüthi |
Date Deposited: |
07 Dec 2022 12:20 |
Last Modified: |
07 Dec 2022 18:38 |
Publisher DOI: |
10.1101/2022.01.27.477992 |
BORIS DOI: |
10.48350/175534 |
URI: |
https://boris.unibe.ch/id/eprint/175534 |
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