Increased Inflammasome Activation Is Associated with Aging and Chronic Myelomonocytic Leukemia Disease Severity.

Andina, Nicola; de Meuron, Louise; Schnegg-Kaufmann, Annatina Sarah; Sarangdhar, Mayuresh Anant; Ansermet, Camille; Bombaci, Giuseppe; Batta, Kiran; Keller, Nino; Porret, Naomi A; Angelillo, Anne; Bonadies, Nicolas; Allam, Ramanjaneyulu (2023). Increased Inflammasome Activation Is Associated with Aging and Chronic Myelomonocytic Leukemia Disease Severity. Journal of immunology, 210(5), pp. 580-589. American Association of Immunologists 10.4049/jimmunol.2200412

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Aging causes chronic low-grade inflammation known as inflamm-aging. It is a risk factor for several chronic disorders, including chronic myelomonocytic leukemia (CMML), a hematological malignancy that is most prevalent in older people. Recent studies suggest a critical role for the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome in inflamm-aging. However, the mechanisms involved in NLRP3 activation in aging and its involvement in CMML progression are not fully understood. In this study, we report that aging increases IL-1β production upon NLRP3 activation in human CD14+ monocytes. Interestingly, we found that the TLR1/2 agonist Pam3CSK4 directly activates the NLRP3 inflammasome in monocytes from older but not from younger healthy donors. Furthermore, we observed a dichotomous response to NLRP3 inflammasome activation in monocytes from a small cohort of CMML patients, and some patients produced high levels of IL-1β and some patients produced low levels of IL-1β compared with older healthy donors. 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 a cellular level, which may explain increased inflammation and immune dysregulation in older individuals. Furthermore, NLRP3 inflammasome activation was dysregulated in a small cohort of CMML patients and was positively correlated with disease severity.

Item Type:

 Journal Article (Original Article)

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)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hämatologie / Onkologie (Pädiatrie)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hämatologie / Onkologie (Pädiatrie)

UniBE Contributor:

 Andina, Nicola, de Meuron, Louise, Schnegg-Kaufmann, Annatina Sara, Sarangdhar, Mayuresh Anant, Ansermet, Camille Eva, Bombaci, Giuseppe, Keller, Nino Raphael, Porret, Naomi, Angelillo, Anne, Bonadies, Nicolas, Allam, Ramanjaneyulu

Subjects:

 600 Technology > 610 Medicine & health

ISSN:

 0022-1767

Publisher:

 American Association of Immunologists

Language:

 English

Submitter:

 Pubmed Import

Date Deposited:

 23 Jan 2023 12:23

Last Modified:

 08 Mar 2023 00:14

Publisher DOI:

 10.4049/jimmunol.2200412

PubMed ID:

 36661356

BORIS DOI:

 10.48350/177717

URI:

 https://boris.unibe.ch/id/eprint/177717

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