P#15   Interleukin-10 knockout mice are relatively resistant to the experimental induction of alopecia areata

Pia Freyschmidt-Paul, Kevin McElwee, Margot Zöller, John Sundberg, Rudolf Happle and Rolf Hoffmann. Philipp University Marburg, Germany; DKFZ, Germany; The Jackson Laboratory, Bar Harbor, USA

Alopecia areata (AA) occurs spontaneously in C3H/HeJ mice, but it can be induced in unaffected C3H/HeJ mice or other histocompatible strains by grafting of AA-affected mouse skin. Because IL-10 expression is increased in scalp from AA-patients, successfully treated with DCP, we wanted to determine whether the absence of IL-10 results in increased susceptibility to the development of AA. For this purpose we tried to induce AA in 20 C3H/HeJBir-Il10-/- mice by skin grafting and as controls we grafted AA-affected skin onto 20 unaffected C3H/HeJ mice. FACS-analysis for a wide panel of cytokines and surface markers was performed on skin-infiltrating leucocytes and cells from skin draining lymph nodes. 13/20 IL-10-/- mice did not develop hair loss, 7/20 IL-10-/- mice developed limited AA, but no mice developed extensive AA. In contrast, 19/20 controls developed AA. FACS-analysis revealed elevated levels of dendritic cells and monocytes in the skin and of dendritic cells in lymph nodes of IL-10-/- mice compared to controls, but a similar level of monocytes in lymph nodes of both groups. IL-10-/- mice had increased levels of IFN-g and TNF-a in lymph nodes and decreased levels of IL-6 in skin. CD25, CD28, CD40, CD80 and CD86 were increased in skin of IL-10-/- mice and CD44s, CD44v3, CD44v6, CD44v7 and CD44v10 were increased in both, skin and lymph nodes of IL-10-/- mice. In a second part of the study, skin from IL-10-/- mice and from C3H/HeJ mice without AA was grafted onto C3H/HeJ mice with extensive AA. AA developed in skin grafts from normal C3H/HeJ mice, but not in skin grafts from IL-10-/- mice. Contrary to expectations we have found that IL-10 deficient mice are relatively resistant to the induction of AA, despite their elevated levels of proinflammatory cytokines and adhesion molecules. Whether the decreased levels of IL-6 could be responsible for the resistance to AA induction requires further investigation.