Ultraviolet-B recruits mannose-binding lectin into skin from non-cutaneous sources.
Mannose-binding lectin (MBL) is an integral part of the innate immune system and functions as an opsonin by binding to pathogens and certain apoptotic cells to promote their uptake by phagocytes. We recently identified an association of low-producing MBL polymorphisms with adult dermatomyositis (DM). Our model is that MBL deficiency leads to a defect in the clearance of apoptotic debris in the skin, thereby predisposing to photosensitive autoimmune disease. In this study, we sought to determine whether MBL binds within the epidermis, and to determine its source, and potential function of this binding. We demonstrated that the MBL is present in irradiated, but not in non-irradiated skin, and in irradiated skin it is bound to apoptotic keratinocytes (KC). We found that MBL is not made by KC, showing indirectly that it comes from an exogenous source, despite the fact that other complement components are made by KC and upregulated by ultraviolet irradiation. Finally, we demonstrated that non-KC-derived MBL bound to apoptotic KC in vitro and increased the uptake of these cells by dendritic cells. We hypothesize that MBL may facilitate non-inflammatory clearance of apoptotic debris in patients with photosensitive forms of DM.
Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Michele L
ML
Lokitz
Wei
W
Zhang
Muhammad
M
Bashir
Kathleen E
KE
Sullivan
Gina
G
Ang
Eun Ji
EJ
Kwon
Julie H
JH
Lin
Victoria P
VP
Werth
D000328:Adult; D017209:Apoptosis / Q000528:radiation effects; D018929:Cell Culture Techniques; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000528:radiation effects*; D037601:Mannose-Binding Lectin / Q000528:radiation effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000528:radiation effects*; D014466:Ultraviolet Rays; D015854:Up-Regulation
D037601:Mannose-Binding Lectin