Patrik Milić (Avtor), Mojca Justin (Avtor), Katerina Jazbec (Avtor), Urban Švajger (Avtor), Primož Rožman (Avtor)

Povzetek

Background: Aging is linked to various dysfunctions of the immune system, including the decline of its primary developmental source: the hematopoietic stem cell (HSC) niche. This decline leads to chronic inflammation, increased vulnerability to infections, cancer, autoimmune diseases, and reduced vaccine efficacy. As individuals age, the HSC niche undergoes significant changes, including greater adipocyte accumulation and alterations in the molecular microenvironment, which may influence the development and function of immune cells. Among these cells, the impact of the aging HSC niche on dendritic cell (DC) function is less understood. Heterochronic autologous HSC transplantation is a promising intervention to prevent age-related disorders, contributing to the extension of healthspan and longevity, however, several murine experiments failed to produce the expected results, which led us to presume that the problem lies within the old HSC niche. Therefore, we created in vitro models of young and old HSC niches and examined how these microenvironments affect the differentiation and maturation and functionality of BM-derived DCs (BMDCs). Results: An analysis of the conditioned media from young and aged HSC niches revealed that the environment of aged niches exhibited an increased presence of adiponectin. This media was subsequently utilized in BMDC differentiation and maturation protocols, with their effects closely monitored. Our results indicate that the old HSC niche microenvironment promotes premature BMDC activation, characterized by elevated MHC class II expression and enhanced allostimulatory capacity of BMDCs at their immature stage. Additionally, LPS stimulation of BMDCs, used to induce DC maturation, significantly increased CD86 expression on BMDCs from the aged niche. However, these cells did not show superior allostimulatory capacity compared to their counterparts from the young niche environment. By analyzing the BMDC cytokine profile, we observed that when cultured in aged niche-conditioned media, the BMDCs secreted significantly higher levels of IL-6, indicating a heightened proinflammatory activation state. Conclusions: Collectively, our findings suggest that aging-related changes within the HSC niche can considerably alter DC functionality by disrupting their normal development from BM precursors. These results emphasize the significance of this phenomenon and its implications for immunosenescence.

Ključne besede

hematopoietic stem cells;HSC niche;inflammation;aging;dendritic cells;bone marrow-derived dendritic cells;BM adipocytes;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FFA - Fakulteta za farmacijo
UDK: 602.9
COBISS: 241473283 Povezava se bo odprla v novem oknu
ISSN: 1742-4933
Št. ogledov: 69
Št. prenosov: 10
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: hematopoetske matične celice;niša HSC;vnetje;staranje;dendritične celice;dendritične celice kostnega mozga;adipociti kostnega mozga;Matične celice;
Vrsta dela (COBISS): Članek v reviji
Strani: 12 str.
Letnik: [article. no.] 26
Zvezek: ǂVol. ǂ22
Čas izdaje: 2025
DOI: 10.1186/s12979-025-00517-9
ID: 27218314