| First Author | Dubrac S | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 7 | Pages | 1980-91 |
| PubMed ID | 21509781 | Mgi Jnum | J:177304 |
| Mgi Id | MGI:5294718 | Doi | 10.1002/eji.201041357 |
| Citation | Dubrac S, et al. (2011) Lack of IL-2 in PPAR-alpha-deficient mice triggers allergic contact dermatitis by affecting regulatory T cells. Eur J Immunol 41(7):1980-91 |
| abstractText | The aim of the present work was to decipher the cellular basis of the immunoregulatory role of peroxisome proliferator-activated receptor (PPAR)-alpha in cutaneous hypersensitivity reactions. After challenge with a contact allergen, we observed augmented hypersensitivity reactions with increased numbers of activated T lymphocytes in the skin of PPAR-alpha-/- mice. Furthermore, following antigen challenge, the percentages of Tregs in the blood, draining lymph nodes and skin were decreased in these mice. PPAR-alpha deficiency impaired the production of IL-2 in lymph nodes, whereas TGF-beta levels remained unchanged. Injection of IL-2 into PPAR-alpha-/- mice restored the Treg population in the skin-draining lymph nodes of allergen-challenged mice. In vivo induction of Tregs from WT CD4+ CD25- T cells was impaired when adoptively transferred into PPAR-alpha-/- mice as compared with transfer into WT mice, and reversed by injection of IL-2 into PPAR-alpha-/- mice. Furthermore, the suppressive capacity of PPAR-alpha-/- Tregs was impaired when compared to WT Tregs in vitro and in co-adoptive transfer experiments. Finally, injection of IL-2 to PPAR-alpha-/- mice decreased skin inflammation to a level similar to WT mice. In conclusion, the pro-inflammatory skin phenotype of PPAR-alpha-/- mice is due to lack of IL-2-mediated Treg induction in these mice. |
