IN HUMAN SKIN, UVB INITIATES EARLY INDUCTION OF IL-10 OVER IL-12 PREFERENTIALLY IN THE EXPANDING DERMAL MONOCYTIC MACROPHAGIC POPULATION/

In contrast to Langerhans cells, which make interleukin (IL)-12, diffe rentiated macrophages that infiltrate the epidermis 72 h after ultravi olet B (UV) irradiation potently produce IL-10 mRNA and secrete IL-10 protein. We asked whether differentiated UV macrophages in the epiderm is acquired their activated, IL-10(hi) status as a result of entering the epidermis or as a result of encountering UV-induced changes in the dermal microenvironment, In this study, sequential section immunostai ning directly showed dynamic and reciprocal changes of infiltrating CD 11b(+) macrophages and CD1a(+) Langerhans cell loss in human epidermis and dermis after in vivo UV exposure in relation to the microanatomic localization of newly appearing dermal cells that stain for IL10 mRNA by in situ hybridization, Using quantitative reverse transcriptase po lymerase chain reaction on purified dermal cell subsets, the first sig nificant rise in IL-10 mRNA occurred 6 h after UV in the dermal CD11b( +) (CD1(-), 3(-), 24(-), 56(-)) monocytic/macrophagic population. Sign ificant induction of IL-10 mRNA 24 h post-UV was limited to the CD11b( +) CD1(-) subset (p = 0,006), The fold increase of IL-10 mRNA relative to 0 h by the CD11b(+) dermal monocytic/macrophagic population peaked at 24-48 h and tapered thereafter. Intense IL-10 production by macrop hages in the epidermis appeared to follow dermal changes, with maximum production at 72 h, indicating migration/activation of this populatio n from the dermis, and the remainder of dermal cells, depleted of mono cyte/macrophages and Langerhans cell-like antigen-presenting cells, sh owed no increase in IL 10 at any time point post-UV, IL-10 protein-pro ducing CD11b(+) macrophages in the dermis were also documented by flow cytometry, IL-12 mRNA was differentially regulated from IL-10 after U V, in that IL-12 was consistently downregulated in the CD11b(+) monocy tic/macrophagic population (p < 0.0002), Taken together, monocytic/mac rophagic cells with high IL-10 and low IL-12 expression initially appe ar in the dermis as early as 6 h, and then appear in the epidermis, im plicating the dermis as the primary site of activation/signaling for I L 10 upregulation in cutaneous antigen-presenting cells.