Systematic name M8079
Brief description Genes down-regulated in lymph node CD4 [GeneID=920] T cells: scurfy (non-functional form of FOXP3 [GeneID=50943]) versus scurfy and IL2 [GeneID=3558] knockout.
Full description or abstract The goal of the study was to identify the genes which are regulated by Interleukin-2 in the CD4+ T cells of the scurfy mice during regulatory T-cell deficiency. Scurfy (Sf) mice bear a mutation in the forkhead box P3 (Foxp3) transcription factor, lack regulatory T-cells (Treg), develop multi-organ inflammation, and die prematurely. The major target organs affected are skin, lungs, and liver. Sf mice lacking the Il2 gene (Sf.Il2-/-), despite devoid of Treg, did not develop skin and lung inflammation, but the inflammation in liver, pancreas, submandibular gland and colon remained. Genome-wide microarray analysis revealed hundreds of genes were differentially regulated among Sf, Sf.Il2-/-, and B6 CD4+ T-cells but the most changes were those encoding receptors for trafficking/chemotaxis/retention and lymphokines. 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 receptors for T-cell trafficking/chemotaxis/retention and by regulating Th2 cell expansion and lymphokine production. Thus, IL-2 is a master regulator for multi-organ inflammation and an underlying etiological factor for various diseases associated with skin and lung inflammation. Methods: CD4+ T cells were purified by Fluorescence Assisted Cell Sorting from the peripheral lymph nodes of (A) three individual Scurfy (Sf; B6.Cg-Foxp3sf/J) male mice, (B) three individual Sf.Il2-/- male mice (Scurfy mice carrying a null Interleukin (IL)-2 gene (B6.129P2-Il2tm1Hor/J)) and (C) a pooled sample of lymph nodes from two B6 (C57BL/6J) mice. All the mice were 3 weeks old. Total RNA was prepared using RNeasy mini kit (Qiagen). RNA samples were converted to cRNA, labeled and hybridized to Affymetrix Mouse 430_2 chips (Mouse Genome 430 2.0 Array, Affymetrix, Santa Clara, CA) at the University of Virginia DNA Sciences Core Facility.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 21169543   Authors: Sharma R,Sharma PR,Kim YC,Leitinger N,Lee JK,Fu SM,Ju ST
Exact source GSE23398_3081_200_DN
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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