Genomic definition of multiple ex vivo regulatory T cell subphenotypes.
Regulatory T (Treg) cells that express the Foxp3 transcription factor are essential for lymphoid homeostasis and immune tolerance to self. Other nonimmunological functions of Treg cells, such as controlling metabolic function in adipose tissue, are also emerging. Treg cells originate primarily in the thymus, but can also be elicited from conventional T cells by in vivo exposure to low-dose antigen or homeostatic expansion or by activation in the presence of TGFbeta in vitro. Treg cells are characterized by a distinct transcriptional signature controlled in part, but not solely, by Foxp3. For a better perspective on transcriptional control in Treg cells, we compared gene expression profiles of a broad panel of Treg cells from various origins or anatomical locations. Treg cells generated by different means form different subphenotypes and were identifiable by particular combinations of transcripts, none of which fully encompassed the entire Treg signature. Molecules involved in Treg cell effector function, chemokine receptors, and the transcription factors that control them were differentially represented in these subphenotypes. Treg cells from the gut proved dissimilar to cells elicited by exposure to TGFbeta in vitro, but instead they resembled a CD103(+)Klrg1(+) subphenotype preferentially generated in response to lymphopenia.
Feuerer
Markus
M
Department of Pathology, Harvard Medical School, and Section on Immunology and Immunogenetics, Joslin Diabetes Center, Boston, MA 02115, USA.
Hill
Jonathan A
JA
Kretschmer
Karsten
K
von Boehmer
Harald
H
Mathis
Diane
D
Benoist
Christophe
C
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D023281:Genomics; D066298:In Vitro Techniques; D039001:Integrin alpha Chains / Q000378:metabolism; D037181:Lectins, C-Type; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011971:Receptors, Immunologic / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000145:classification* / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000145:classification* / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D015703:Antigens, CD; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D039001:Integrin alpha Chains; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D016212:Transforming Growth Factor beta; C091367:alpha E integrins