T-bet-dependent expression of osteopontin contributes to T cell polarization.
The osteopontin (Opn) glycoprotein has been implicated in diverse physiological processes, including vascularization, bone formation, and inflammatory responses. Studies of its role in immune responses has suggested that Opn can set the early stage of type-1 immune (cell-mediated) responses through differential regulation of IL-12 and IL-10 cytokine gene expression in macrophages. Although Opn has been suggested to play a role in the development of type-1 immunity, little is known about control of Opn gene expression. Here, we report that Opn gene expression in activated T cells, but not macrophages, is regulated by T-bet, a transcription factor that controls CD4+ T helper (Th1) cell lineage commitment. We also find that T-bet-dependent expression of Opn in T cells is essential for efficient skewing of CD4+ T and CD8+ T cells toward the Th1 and type 1 CD8+ T cells (Tc1) pathway, respectively. Taken together, these findings begin to delineate the genetic basis of Opn expression in T cells and further clarify the role of Opn in Th and Tc1 development.
Shinohara
Mari L
ML
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Jansson
Marianne
M
Hwang
Eun Sook
ES
Werneck
Miriam B F
MB
Glimcher
Laurie H
LH
Cantor
Harvey
H
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D020825:T-Box Domain Proteins; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000098815:T-bet Transcription Factor
D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D053495:Osteopontin