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

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, pancreas, submandibular gland, and colon remained. 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. The Journal of Immunology, 2011, 186: 1268-1278.