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Войти в исследования Kidney360 · 2026
The Kinetics and Mechanism of Niche Filling in Healthy and Cystic Mice.
СтатьяНазвание и аннотация: Перевод в очереди
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Yashchenko Alex, Miller Sarah J, Cordova Audrey M, Yashchenko Morgan E, Khan Shuja, Maryam Bibi, Darby Isabella G, Park Yohan, Nusrat Fariha, Ahmed Ummey Khalecha Bintha, Zimmerman Kurt A
Аннотация
KEY POINTS: The rate and mechanism of kidney-resident macrophage niche filling differs between healthy and cystic mice. An incompletely filled kidney-resident macrophage niche is associated with worsened polycystic kidney disease outcomes.
BACKGROUND: Previous data indicate that bone marrow-derived Ly6c hi monocytes can become tissue-resident macrophages when the niche is available. However, the balance between monocyte recruitment and tissue-resident macrophage self-proliferation following partial depletion is unclear.
METHODS: We investigated the kinetics and mechanism of kidney-resident macrophage (KRM) niche filling in healthy mice and in a mouse model of autosomal dominant polycystic kidney disease after partial depletion with liposomal clodronate.
RESULTS: Our data indicate that healthy mice efficiently refilled their KRM niche through monocyte-dependent recruitment, engraftment, and differentiation while cystic mice relied preferentially on in situ KRM self-proliferation for niche filling. Furthermore, we found sex-specific differences in niche-filling capacity in cystic mice as female, but not male, mice were unable to completely fill their niche 90 days postdepletion. The inability of cystic female mice to fill the niche following depletion was likely due to their reduced ability to recruit monocytes and convert them into KRM. Phenotypically, delayed KRM niche filling was associated with worsened outcomes including increased cystic index and kidney fibrosis as well as worsened kidney function.
CONCLUSIONS: Collectively, our data demonstrate that sex and disease status affect the kinetics and mechanism of niche filling in the kidney.
BACKGROUND: Previous data indicate that bone marrow-derived Ly6c hi monocytes can become tissue-resident macrophages when the niche is available. However, the balance between monocyte recruitment and tissue-resident macrophage self-proliferation following partial depletion is unclear.
METHODS: We investigated the kinetics and mechanism of kidney-resident macrophage (KRM) niche filling in healthy mice and in a mouse model of autosomal dominant polycystic kidney disease after partial depletion with liposomal clodronate.
RESULTS: Our data indicate that healthy mice efficiently refilled their KRM niche through monocyte-dependent recruitment, engraftment, and differentiation while cystic mice relied preferentially on in situ KRM self-proliferation for niche filling. Furthermore, we found sex-specific differences in niche-filling capacity in cystic mice as female, but not male, mice were unable to completely fill their niche 90 days postdepletion. The inability of cystic female mice to fill the niche following depletion was likely due to their reduced ability to recruit monocytes and convert them into KRM. Phenotypically, delayed KRM niche filling was associated with worsened outcomes including increased cystic index and kidney fibrosis as well as worsened kidney function.
CONCLUSIONS: Collectively, our data demonstrate that sex and disease status affect the kinetics and mechanism of niche filling in the kidney.