Transcription factor KLF2 regulates the migration of naive T cells by restricting chemokine receptor expression patterns.
The migration patterns of naive and activated T cells are associated with the expression of distinct sets of chemokine receptors, but the molecular basis for this regulation is unknown. Here we identify Krupple-like factor 2 (KLF2) as a key transcriptional factor needed to prevent naive T cells from expressing inflammatory chemokine receptors and acquiring the migration patterns of activated T cells. Lineage-specific deletion of KLF2 resulted in fewer naive T cells in the blood and secondary lymphoid organs, whereas it expanded naive T cell numbers in nonlymphoid tissues; these effects were associated with altered expression of inflammatory chemokine receptors on naive T cells. KLF2 repressed the expression of several chemokine receptors, including CCR3 and CCR5. We thus conclude that KLF2 maintains proper T cell migration patterns by linking T cell movement and transcriptional regulation of chemokine receptor expression patterns.
Sebzda
Eric
E
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. eric.sebzda@vanderbilt.edu
Zou
Zhiying
Z
Lee
John S
JS
Wang
Tao
T
Kahn
Mark L
ML
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D054397:Receptors, CCR3 / Q000235:genetics / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*
C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019713:Receptors, CCR5