Skin-infiltrating monocytes/macrophages migrate to draining lymph nodes and produce IL-10 after contact sensitizer exposure to UV-irradiated skin.
Low-dose UVB exposure induces antigen-specific unresponsiveness to antigen(s) introduced through UV-irradiated skin (tolerance). Analysis of cytokine expression in murine draining lymph nodes (DLNs) revealed that IL-12p40 mRNA and protein expression as well as IL-12p70 protein were upregulated after application of the contact sensitizer 2,4 dinitro-1-fluorobenzene (DNFB) to normal skin. The cellular source of IL-12p40 mRNA was CD11c+ cells. By contrast, following DNFB application to UV-irradiated skin (UV+DNFB), IL-12p40 mRNA was not upregulated, and DLN IL-12p40 and p70 proteins were reduced. UVB irradiation alone did not upregulate IL-10 mRNA, but UV+DNFB upregulated IL-10 mRNA as early as 3-6 hours after DNFB application, immediately preceding a decrease of IL-12p40 mRNA from the level induced by UVB. The infiltration of F4/80+ cells into UV-irradiated skin was followed by a rapid and remarkable increase of F4/80+CD11c(-) cells in DLN 3 hours following DNFB application. FITC/DNFB skin painting and subsequent enzyme-linked immunospot assay demonstrated that flow-sorted FITC+F4/80+CD11c(-) cells from the DLN produce IL-10. Thus, monocytes/macrophages that infiltrated into the skin following UVB exposure migrate to the DLN triggered by contact sensitizers. Production of IL-10 by migrating macrophages, in conjunction with IL-12 inhibition in the DLN, likely reflects a role as mobile suppressive mediators for locally induced UV tolerance.
Department of Dermatology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, USA; Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Eiko
E
Toichi
Department of Dermatology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, USA.
Kurt Q
KQ
Lu
Department of Dermatology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, USA.
Alan R
AR
Swick
Department of Dermatology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, USA.
Thomas S
TS
McCormick
Department of Dermatology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, USA; Department of Dermatology, Veterans Administration Medical Center, Cleveland, Ohio, USA. Electronic address: kdc@case.edu.
Kevin D
KD
Cooper
D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000528:radiation effects*; D004139:Dinitrofluorobenzene / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
D039521:CD11c Antigen; D053762:Interleukin-12 Subunit p40; D012333:RNA, Messenger; D016753:Interleukin-10; D004139:Dinitrofluorobenzene