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Journal of Investigative Dermatology

Monocytes and their derived cells have critical roles in inflflammation and immune defense. However, their function in skin diseases such as allergic contact dermatitis remains poorly defifined. Using a model of contact hypersensitivity (CHS) toward 2,4-dinitrochlorobenzene, we show that Ly6C⁺CD11b⁺ monocytic cells participate in the pathophysiology of CHS and their accumulation is regulated by effector CD8 T cells. These Ly6C⁺CD11b⁺ monocytic cells are the primary contributors of tumor necrosis factor-a (TNF-a) and inducible nitric oxide synthase (iNOS) and derive from Ly6C^hiCCR2⁺monocytes, as they were absent in non-inflflamed skin and accumulate as a consequence of inflflammation in a C–C chemokine receptor type 2 (CCR2)–dependent manner. Importantly, CCR2 ^-/- mice, or wild-type mice depleted of monocytes via clodronate liposomes, display a marked decrease in TNF-a and iNOS expression accompanied by attenuated skin inflflammation. Using transgenic mice and antibody depletion, we show that effector CD8 T cells regulate the accumulation of Ly6C⁺CD11b⁺ monocytic cells through IL-17 and activate them for TNF-a and iNOS through IFN-g. CD8 T cell–derived IFN-g was also critical for the accumulation of the major histocompatibility complex II–expressing Ly6C⁺CD11b⁺ subset, which expressed intermediate levels of CD11c and costimulatory molecules. Taken together, our fifindings provide further insight into the pathophysiology of allergic contact dermatitis by showing that CD8 T cells regulate the inflflammatory cascade through TNF/iNOS–expressing Ly6C⁺CD11b⁺ monocytic cells.