Transcriptional downregulation of S1pr1 is required for the establishment of resident memory CD8+ T cells

被引:616
作者
Skon, Cara N. [1 ]
Lee, June-Yong [1 ]
Anderson, Kristin G. [2 ]
Masopust, David [2 ]
Hogquist, Kristin A. [1 ]
Jameson, Stephen C. [1 ]
机构
[1] Univ Minnesota, Dept Lab Med & Pathol, Ctr Immunol, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Dept Microbiol, Ctr Immunol, Minneapolis, MN 55455 USA
基金
美国国家卫生研究院;
关键词
KRUPPEL-LIKE FACTOR-2; LYMPHOCYTE EGRESS; CUTTING EDGE; RM CELLS; TISSUE; INFECTION; EFFECTOR; DIFFERENTIATION; TRAFFICKING; EXPRESSION;
D O I
10.1038/ni.2745
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cell-mediated immunity critically depends on the localization of lymphocytes at sites of infection. While some memory T cells recirculate, a distinct lineage (resident memory T cells (T-RM cells)) are embedded in nonlymphoid tissues (NLTs) and mediate potent protective immunity. However, the defining transcriptional basis for the establishment of T-RM cells is unknown. We found that CD8(+) T-RM cells lacked expression of the transcription factor KLF2 and its target gene S1pr1 (which encodes S1P(1), a receptor for sphingosine 1-phosphate). Forced expression of S1P(1) prevented the establishment of T-RM cells. Cytokines that induced a T-RM cell phenotype (including transforming growth factor-beta (TGF-beta), interleukin 33 (IL-33) and tumor-necrosis factor) elicited downregulation of KLF2 expression in a pathway dependent on phosphatidylinositol-3-OH kinase (PI(3) K) and the kinase Akt, which suggested environmental regulation. Hence, regulation of KLF2 and S1P(1) provides a switch that dictates whether CD8(+) T cells commit to recirculating or tissue-resident memory populations.
引用
收藏
页码:1285 / +
页数:11
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