Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes

被引：222

作者：

Elyahu, Yehezqel ^{[1
,2
,3
,4
]}

Hekselman, Idan ^{[4
,5
]}

Eizenberg-Magar, Inbal ^{[6
]}

Berner, Omer ^{[1
,2
,3
,4
]}

Strominger, Rai ^{[1
,2
,3
,4
]}

Schiller, Maya ^{[7
,8
,9
]}

Mittal, Kritika ^{[1
,2
,3
,4
]}

Nemirovsky, Anna ^{[1
,2
,3
,4
]}

Eremenko, Ekaterina ^{[1
,2
,3
,4
]}

Vital, Assaf ^{[4
,5
]}

Monovsky, Eya I. Si ^{[4
,5
]}

Chalifa-Caspi, Vered ^{[4
]}

Friedman, Nir ^{[6
]}

Yeger-Lotem, Esti ^{[4
,5
]}

Monsonego, Alon ^{[1
,2
,3
,4
]}

机构：

[1] Ben Gurion Univ Negev, Fac Hlth Sci, Shraga Segal Dept Microbiol Immunol & Genet, IL-8410501 Beer Sheva, Israel

[2] Ben Gurion Univ Negev, Zlotowski Neurosci Ctr, Beer Sheva, Israel

[3] Ben Gurion Univ Negev, Regenerat Med & Stem Cell Res Ctr, Beer Sheva, Israel

[4] Ben Gurion Univ Negev, Natl Inst Biotechnol Negev, Beer Sheva, Israel

[5] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Biochem & Pharmacol, Beer Sheva, Israel

[6] Weizmann Inst Sci, Dept Immunol, IL-7610001 Rehovot, Israel

[7] Technion Israel Inst Technol, Rappaport Fac Med, Dept Immunol, IL-3525422 Haifa, Israel

[8] Technion Israel Inst Technol, Rappaport Fac Med, Dept Neurosci, IL-3525422 Haifa, Israel

[9] Technion Israel Inst Technol, Integrated Canc Ctr, IL-3525422 Haifa, Israel

来源：

SCIENCE ADVANCES | 2019年 / 5卷 / 08期

基金：

以色列科学基金会;

关键词：

IMMUNE-SYSTEM; AGE; EXPRESSION; DIFFERENTIATION; ACTIVATION; SENESCENCE; INSIGHTS; INCREASE;

D O I：

10.1126/sciadv.aaw8330

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Age-associated changes in CD4 T-cell functionality have been linked to chronic inflammation and decreased immunity. However, a detailed characterization of CD4 T cell phenotypes that could explain these dysregulated functional properties is lacking. We used single-cell RNA sequencing and multidimensional protein analyses to profile thousands of CD4 T cells obtained from young and old mice. We found that the landscape of CD4 T cell subsets differs markedly between young and old mice, such that three cell subsets-exhausted, cytotoxic, and activated regulatory T cells (aTregs)-appear rarely in young mice but gradually accumulate with age. Most unexpected were the extreme pro-and anti-inflammatory phenotypes of cytotoxic CD4 T cells and aTregs, respectively. These findings provide a comprehensive view of the dynamic reorganization of the CD4 T cell milieu with age and illuminate dominant subsets associated with chronic inflammation and immunity decline, suggesting new therapeutic avenues for age-related diseases.

引用

页数：14

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