title: Lack of IL-2 in PPAR-α-deficient mice triggers allergic contact dermatitis by affecting regulatory T cells.
abstract: The aim of the present work was to decipher the cellular basis of the immunoregulatory role of peroxisome proliferator-activated receptor (PPAR)-α 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-α-/- mice. Furthermore, following antigen challenge, the percentages of Tregs in the blood, draining lymph nodes and skin were decreased in these mice. PPAR-α deficiency impaired the production of IL-2 in lymph nodes, whereas TGF-β levels remained unchanged. Injection of IL-2 into PPAR-α-/- 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-α-/- mice as compared with transfer into WT mice, and reversed by injection of IL-2 into PPAR-α-/- mice. Furthermore, the suppressive capacity of PPAR-α-/- Tregs was impaired when compared to WT Tregs in vitro and in co-adoptive transfer experiments. Finally, injection of IL-2 to PPAR-α-/- mice decreased skin inflammation to a level similar to WT mice. In conclusion, the pro-inflammatory skin phenotype of PPAR-α-/- mice is due to lack of IL-2-mediated Treg induction in these mice.
authors.affiliation: Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria. sandrine.dubrac@i-med.ac.at
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dubrac
authors.forename: Andreas
authors.initials: A
authors.lastname: Elentner
authors.forename: Kristina
authors.initials: K
authors.lastname: Schoonjans
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmuth
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D053804:Granzymes / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000172:deficiency* / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047493:PPAR alpha / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D054353:Perforin / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D047493:PPAR alpha; D054353:Perforin; D016753:Interleukin-10; D053804:Granzymes