Analysis of capturing skin antigens in the steady state using milk fat globule EGF factor 8-deficient...

Dendritic cells (DCs) can capture apoptotic cells and present them to immune competent cells as self-antigens (Ags). Langerhans cells (LCs), DCs in the epidermis, are capable of presenting tissue-associated Ags in the steady state, suggesting that LCs may also capture apoptotic cells and transport them to skin regional lymph nodes (LNs). However, to what extent LCs utilize apoptotic cells as self-Ags in vivo is still unclear. To clarify this point, we examined the contribution of milk fat globule EGF factor 8 (MFG-E8), a secreted glycoprotein, to capturing skin Ags. MFG-E8 is expressed in several subsets of macrophages (M phi s) and DCs, including LCs, and crucial for recognizing and engulfing apoptotic cells. Using a skin-hyperpigmented KRT14-Kitl-Tg (Kitl-Tg) mouse system, we measured the accumulation of melanin granules (MGs), a marker of skin Ags, transported from the skin to regional LNs in Mfge8-deficient mice. Unexpectedly, their accumulation in Mfge8-deficient Kitl-Tg mice was comparable to that in Mfge8-heterozygous littermates. Mfge8-deficient DCs engulfed skin-derived MGs efficiently in vitro. The results indicate that MFG-E8 does not contribute critically or functions redundantly to capturing and trafficking of skin Ags in the steady state, and suggest a possibility that LCs may capture skin Ags in forms other than apoptotic cells in vivo.