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老年小鼠的免疫差异有助于皮肤同种异体移植物的存活。

Immunological discrepancy in aged mice facilitates skin allograft survival.

机构信息

Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan.

出版信息

Aging (Albany NY). 2021 Jun 22;13(12):16219-16228. doi: 10.18632/aging.203152.

DOI:10.18632/aging.203152
PMID:34157682
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8266325/
Abstract

More and more aged people are undergoing organ transplantation. Understanding aging effects on immunity will be helpful for post-transplantation care and adjustment of immunosuppressants for aged recipients. A mouse model, using C3H mice as donors and aged/young C57BL/10J mice as recipients, was employed to study aging effects on immunity. The results showed that frequency of myeloid-derived suppressor cells (MDSC) and level of TGF-β was higher in aged mice than in young mice (4.4 ± 1.4% versus 1.6 ± 1.1%, = 0.026 for MDSC; 21.04 ± 3.91 ng/ml versus 15.26 ± 5.01 ng/ml, = 0.026 for TGF-β). , skin allograft survived longer on the aged than on young mice (19.7 ± 5.2 days versus 11.9 ± 4.1 days, = 0.005). When entinostat was applied to block MDSC, the survival of skin allografts on aged mice was shorten to 13.5 ± 4.7 days which was not different from the survival on young mice (p = 0.359). In conclusion, allogeneic immunity was different in aged from young mice in high frequency of MDSC and high serum level of TGF-β. Blocking the function of MDSC reversed the low immunity in aged mice and caused skin allograft rejection similar to young recipients.

摘要

越来越多的老年人接受器官移植。了解衰老对免疫的影响将有助于老年人接受者的移植后护理和免疫抑制剂的调整。本研究构建了一个以 C3H 小鼠作为供体,老年/年轻 C57BL/10J 小鼠作为受者的小鼠模型,研究衰老对免疫的影响。结果显示,老年小鼠骨髓来源的抑制细胞(MDSC)的频率和 TGF-β 的水平高于年轻小鼠(4.4 ± 1.4%比 1.6 ± 1.1%, = 0.026 用于 MDSC;21.04 ± 3.91 ng/ml 比 15.26 ± 5.01 ng/ml, = 0.026 用于 TGF-β)。老年小鼠皮肤移植物的存活时间长于年轻小鼠(19.7 ± 5.2 天比 11.9 ± 4.1 天, = 0.005)。当应用entinostat 阻断 MDSC 时,老年小鼠皮肤移植物的存活时间缩短至 13.5 ± 4.7 天,与年轻小鼠的存活时间无差异(p = 0.359)。总之,老年小鼠与年轻小鼠相比,具有更高频率的 MDSC 和更高水平的血清 TGF-β,其同种异体免疫存在差异。阻断 MDSC 的功能可逆转老年小鼠的低免疫状态,并导致皮肤移植物排斥反应类似于年轻受者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6184/8266325/4a5b19fd0bea/aging-13-203152-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6184/8266325/c373094268c0/aging-13-203152-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6184/8266325/bc178f35e00b/aging-13-203152-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6184/8266325/f0cec1c11668/aging-13-203152-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6184/8266325/5b91adb40472/aging-13-203152-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6184/8266325/28443b81f2c3/aging-13-203152-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6184/8266325/4a5b19fd0bea/aging-13-203152-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6184/8266325/c373094268c0/aging-13-203152-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6184/8266325/bc178f35e00b/aging-13-203152-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6184/8266325/f0cec1c11668/aging-13-203152-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6184/8266325/5b91adb40472/aging-13-203152-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6184/8266325/28443b81f2c3/aging-13-203152-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6184/8266325/4a5b19fd0bea/aging-13-203152-g006.jpg

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The role of TGF-beta signaling in dendritic cell tolerance.TGF-β 信号在树突状细胞耐受中的作用。
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