Details

Autor(en) / Beteiligte

• Hall, Brandon M.
• Gleiberman, Anatoli S.
• Strom, Evguenia
• Krasnov, Peter A.
• Frescas, David
• Vujcic, Slavoljub
• Leontieva, Olga V.
• Antoch, Marina P.
• Kogan, Valeria
• Koman, Igor E.
• Zhu, Yi
• Tchkonia, Tamara
• Kirkland, James L.
• Chernova, Olga B.
• Gudkov, Andrei V.

Titel

Immune checkpoint protein VSIG4 as a biomarker of aging in murine adipose tissue

Ist Teil von

• Aging cell, 2020-10, Vol.19 (10), p.e13219-n/a

Ort / Verlag

England: John Wiley & Sons, Inc

Erscheinungsjahr

2020

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• Adipose tissue is recognized as a major source of systemic inflammation with age, driving age‐related tissue dysfunction and pathogenesis. Macrophages (Mφ) are central to these changes yet adipose tissue Mφ (ATMs) from aged mice remain poorly characterized. To identify biomarkers underlying changes in aged adipose tissue, we performed an unbiased RNA‐seq analysis of ATMs from young (8‐week‐old) and healthy aged (80‐week‐old) mice. One of the genes identified, V‐set immunoglobulin‐domain‐containing 4 (VSIG4/CRIg), encodes a Mφ‐associated complement receptor and B7 family‐related immune checkpoint protein. Here, we demonstrate that Vsig4 expression is highly upregulated with age in perigonadal white adipose tissue (gWAT) in two mouse strains (inbred C57BL/6J and outbred NIH Swiss) independent of gender. The accumulation of VSIG4 was mainly attributed to a fourfold increase in the proportion of VSIG4+ ATMs (13%–52%). In a longitudinal study, VSIG4 expression in gWAT showed a strong correlation with age within a cohort of male and female mice and correlated strongly with physiological frailty index (PFI, a multi‐parameter assessment of health) in male mice. Our results indicate that VSIG4 is a novel biomarker of aged murine ATMs. VSIG4 expression was also found to be elevated in other aging tissues (e.g., thymus) and was strongly induced in tumor‐adjacent stroma in cases of spontaneous and xenograft lung cancer models. VSIG4 expression was recently associated with cancer and several inflammatory diseases with diagnostic and prognostic potential in both mice and humans. Further investigation is required to determine whether VSIG4‐positive Mφ contribute to immunosenescence and/or systemic age‐related deficits. Adipocytes were removed from gonadal fat (gWAT) of old and young mice, and remaining cells were fractionated into cells capable (e.g., Mφ) and incapable of phagocyting magnetic iron particles. RNA was sequenced and analyzed to identify aging‐associated macrophage‐specific transcripts. Identified candidates were validated, and VSIG4 was confirmed a macrophageal biomarker correlating with chronological and biological age.