The Bone Marrow Protects and Optimizes Immunological Memory during Dietary Restriction

被引：165

作者：

Collins, Nicholas ^{[1
]}

Han, Seong-Ji ^{[1
]}

Enamorado, Michel ^{[1
]}

Link, Verena M. ^{[1
]}

Huang, Bonnie ^{[2
]}

Moseman, E. Ashley ^{[3
]}

Kishton, Rigel J. ^{[4
]}

Shannon, John P. ^{[5
]}

Dixit, Dhaval ^{[6
]}

Schwab, Susan R. ^{[6
]}

Hickman, Heather D. ^{[5
]}

Restifo, Nicholas P. ^{[4
]}

McGavern, Dorian B. ^{[3
]}

Schwartzberg, Pamela L. ^{[2
]}

Belkaid, Yasmine ^{[1
]}

机构：

[1] NIAID, Metaorganism Immun Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[2] NIH, Cell Signaling Sect, Lab Immune Syst Biol, Bethesda, MD 20892 USA

[3] NINDS, Viral Immunol & Intravital Imaging Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA

[4] NCI, Surg Branch, NIH, Bethesda, MD 20814 USA

[5] NIAID, Viral Immun & Pathogenesis Unit, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[6] NYU, Skirball Inst Biomol Med, Sch Med, New York, NY 10016 USA

来源：

CELL | 2019年 / 178卷 / 05期

关键词：

T-CELL MEMORY; LYMPHOCYTE EGRESS; ADIPOSE-TISSUE; SELF-RENEWAL; METABOLISM; RESERVOIR; EFFECTOR; SUBSETS; BLOOD; MICE;

D O I：

10.1016/j.cell.2019.07.049

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Mammals evolved in the face of fluctuating food availability. How the immune system adapts to transient nutritional stress remains poorly understood. Here, we show that memory T cells collapsed in secondary lymphoid organs in the context of dietary restriction (DR) but dramatically accumulated within the bone marrow (BM), where they adopted a state associated with energy conservation. This response was coordinated by glucocorticoids and associated with a profound remodeling of the BM compartment, which included an increase in T cell homing factors, erythropoiesis, and adipogenesis. Adipocytes, as well as CXCR4-CXCL12 and S1P-S1P(1)R interactions, contributed to enhanced T cell accumulation in BM during DR. Memory T cell homing to BM during DR was associated with enhanced protection against infections and tumors. Together, this work uncovers a fundamental host strategy to sustain and optimize immunological memory during nutritional challenges that involved a temporal and spatial reorganization of the memory pool within ''safe haven'' compartments.

引用

页码：1088 / +

页数：29

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