F17 CHARACTERIZING C3H/HeJ MICE WITH APPARENT RESISTANCE TO ALOPECIA AREATA ONSET

¹McElwee KJ., ²Zöller M., ¹Wenzel E., ¹Freyschmidt-Paul P., ³Sundberg JP., ¹Hoffmann R. ¹Philipp University, Marburg; ²DKFZ, Heidelberg, Germany; ³The Jackson Laboratory, Bar Harbor, ME, USA.

Spontaneous alopecia areata (AA) develops in up to 20% of C3H/HeJ mice. The disease can also be induced in normal haired mice by grafting AA affected skin to their dorsal surface. Dietary Soy oil content and other, as yet unidentified, environmental factors can reduce host susceptibility to AA onset after grafting. Mice which failed to develop AA after grafting were characterized by gross observation, by adoptive transfer of lymphocytes and FACS analysis of skin, lymph nodes and spleen cells.

Twelve mice that received AA affected skin grafts but failed to develop AA received additional AA affected skin grafts 12 or more weeks after the initial surgery. Eleven of 12 developed no overt hair loss. Histology of apparently unaffected mice revealed isolated, individual anagen hair follicles to be inflamed but the majority of hair follicles showed normal morphologic features and no inflammation.  In contrast, 8 of 12 control mice grafted with skin from the same donors developed AA.

Subcutaneous injection of 10⁷ lymph node or spleen cells from grafted mice that failed to develop AA to 10 normal haired mice did not induce AA. Transfer of lymph node and spleen cells combined to 8 normal haired mice three weeks prior to grafting AA affected skin did not significantly increase resistance to AA onset as 4 of 8 mice developed AA. FACS analysis revealed AA affected mice had an increased percentage of CD4⁺, CD8⁺ and sIgM⁺ cells in the skin and increased numbers of monocytes and dendritic cells, plus strong upregulation of CD44v3, in skin draining lymph nodes in comparison to control mice. In contrast, resistant mice showed very low expression of the leukocyte activation marker CD25 and a strong downmodulation of CD44v3, CD44v7 and CD44v10 in lymph nodes.

The results suggest that exposure to a variety of factors in AA affected skin grafts promotes disease onset or resistance to AA depending on the environment in which the stimulatory factors are presented.