A Prominent Pro-Inflammatory Phenotype Is Observed in Replication and Stress-Induced Senescent Mast Cells.

Area of Science:

• Immunology
• Cell Biology
• Aging Research

Background:

• Mast cells (MCs) are crucial immune cells involved in inflammation and allergies.
• The impact of replicative and stress-induced senescence on MCs and its in vivo relevance remain largely undescribed.
• Understanding MC senescence is vital for comprehending age-related inflammatory diseases.

Purpose of the Study:

• To investigate senescence markers in replicative and stress-induced senescent mast cells.
• To determine how senescence affects mast cell function and activation.
• To explore the role of senescent mast cells in aging-associated inflammation.

Main Methods:

• Generated senescent bone marrow-derived mast cells (BMMCs) through long-term culture or LPS treatment.
• Assessed senescence markers including p16INK4A, p21CIP1/WAF1, cell cycle arrest, and SA-β-Gal activity.
• Utilized MC-deficient mice reconstituted with MCs to study in vivo responses to LPS.

Main Results:

• Senescence markers were observed in both replicative and stress-induced senescent MCs.
• Senescence altered MC metabolism, reduced maximal FcεRI and TLR4-dependent activation, and induced a SASP including IL-23, IL-6, and VEGF.
• Senescent MCs exhibited exacerbated cytokine production in vivo, and MCs from chronically LPS-treated animals showed high basal cytokine production.

Conclusions:

• Senescence significantly impacts mast cell phenotype and function.
• Altered mast cell function due to senescence contributes to increased inflammatory responses in aging.
• These findings suggest a role for senescent mast cells in inflammaging.