The Bone Marrow Protects and Optimizes Immunological Memory during Dietary Restriction.

TitleThe Bone Marrow Protects and Optimizes Immunological Memory during Dietary Restriction.
Publication TypeJournal Article
Year of Publication2019
AuthorsCollins, N, Han, S-J, Enamorado, M, Link, VM, Huang, B, E Moseman, A, Kishton, RJ, Shannon, JP, Dixit, D, Schwab, SR, Hickman, HD, Restifo, NP, McGavern, DB, Schwartzberg, PL, Belkaid, Y
JournalCell
Volume178
Issue5
Pagination1088-1101.e15
ISSN1097-4172
KeywordsAnimals, Bone Marrow, Caloric Restriction, CD8-Positive T-Lymphocytes, Cell Line, Tumor, Chemokine CXCL12, Diet, Reducing, Energy Metabolism, Gene Expression Regulation, Glucocorticoids, Immunologic Memory, Melanoma, Experimental, Mice, Mice, Inbred C57BL, Proto-Oncogene Proteins c-akt, Receptors, CXCR4, Survival Rate, T-Lymphocytes, TOR Serine-Threonine Kinases
Abstract

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-S1P1R 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.

DOI10.1016/j.cell.2019.07.049
Alternate JournalCell