title: IL-2-controlled expression of multiple T cell trafficking genes and Th2 cytokines in the regulatory T cell-deficient scurfy mice: implication to multiorgan inflammation and control of skin and lung inflammation.
abstract: Scurfy (Sf) mice bear a mutation in the Foxp3 transcription factor, lack regulatory T cells (Treg), develop multiorgan inflammation, and die prematurely. The major target organs affected are skin, lungs, and liver. “Sf mice lacking the Il2 gene (Sf.Il2–/–), despite being devoid of Treg, did not develop skin and lung inflammation, but the inflammation in liver remained [corrected]. Genome-wide microarray analysis revealed hundreds of genes that were differentially regulated among Sf, Sf.Il2(-/-), and B6 CD4(+) T cells, but the most significant changes were those encoding receptors for trafficking/chemotaxis/retention and cytokines. Our study suggests that IL-2 controls the skin and lung inflammation in Sf mice in an apparent "organ-specific" manner through two novel mechanisms: by regulating the expression of genes encoding a variety of receptors for T cell trafficking/chemotaxis/retention and by regulating Th2 cell expansion and cytokine production. Thus, IL-2 is potentially a master regulator for multiorgan inflammation and an underlying etiological factor for various diseases associated with skin and lung inflammation.
authors.affiliation: Department of Medicine, Center for Immunity, Inflammation and Regenerative Medicine, University of Virginia, Charlottesville, VA 22908, USA. rs3wn@virginia.edu
authors.forename: Rahul
authors.initials: R
authors.lastname: Sharma
authors.forename: Poonam R
authors.initials: PR
authors.lastname: Sharma
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Norbert
authors.initials: N
authors.lastname: Leitinger
authors.forename: Jae K
authors.initials: JK
authors.lastname: Lee
authors.forename: Shu Man
authors.initials: SM
authors.lastname: Fu
authors.forename: Shyr-Te
authors.initials: ST
authors.lastname: Ju
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009102:Multiple Organ Failure / Q000235:genetics / Q000276:immunology / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D007376:Interleukin-2