| First Author | Chong SZ | Year | 2014 |
| Journal | J Invest Dermatol | Volume | 134 |
| Issue | 3 | Pages | 666-676 |
| PubMed ID | 24061165 | Mgi Jnum | J:206039 |
| Mgi Id | MGI:5547683 | Doi | 10.1038/jid.2013.403 |
| Citation | Chong SZ, et al. (2014) CD8 T Cells Regulate Allergic Contact Dermatitis by Modulating CCR2-Dependent TNF/iNOS-Expressing Ly6C(+)CD11b(+) Monocytic Cells. J Invest Dermatol 134(3):666-76 |
| abstractText | Monocytes and their derived cells have critical roles in inflammation and immune defense. However, their function in skin diseases such as allergic contact dermatitis remains poorly defined. 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-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) and derive from Ly6C(hi)CCR2(+) monocytes, as they were absent in non-inflamed skin and accumulate as a consequence of inflammation 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-alpha and iNOS expression accompanied by attenuated skin inflammation. 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-alpha and iNOS through IFN-gamma. CD8 T cell-derived IFN-gamma 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 findings provide further insight into the pathophysiology of allergic contact dermatitis by showing that CD8 T cells regulate the inflammatory cascade through TNF/iNOS-expressing Ly6C(+)CD11b(+) monocytic cells. |
