Dermal gamma delta T Cells Do Not Freely Re-Circulate Out of Skin and Produce IL-17 to Promote Neutrophil Infiltration during Primary Contact Hypersensitivity

作者：Jiang Xiaodong; Park Chang Ook; Sweeney Jenna Geddes; Yoo Min Jae; Gaide Olivier; Kupper Thomas Seth^*

来源：PLos One, 2017, 12(1): e0169397.

DOI：10.1371/journal.pone.0169397

The role of mouse dermal gamma delta T cells in inflammatory skin disorders and host defense has been studied extensively. It is known that dendritic epidermal T cells (DETC) have a monomorphic gamma delta T cell receptor (TCR) and reside in murine epidermis from birth. We asked if dermal gamma delta cells freely re-circulated out of skin, or behaved more like dermal resident memory T cells (T-RM) in mice. We found that, unlike epidermal gamma delta T cells (DETC), dermal gamma delta cells are not homogeneous with regard to TCR, express the tissue resident T cell markers CD69 and CD103, bear skin homing receptors, and produce IL-17 and IL-22. We created GFP(+): GFP(-) parabiotic mice and found that dermal gamma delta T cells re-circulate very slowly-more rapidly than authentic alpha beta TCR T-RM, but more slowly than the recently described dermal alpha beta TCR T migratory memory cells (T-MM). Mice lacking the TCR delta gene (delta(-/-)) had a significant reduction of 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity (CHS). We created mice deficient in dermal gamma delta T cells but not DETC, and these mice also showed a markedly reduced CHS response after DNFB challenge. The infiltration of effector T cells during CHS was not reduced in dermal gamma delta T cell-deficient mice; however, infiltration of Gr-1(+) CD11b(+) neutrophils, as well as ear swelling, was reduced significantly. We next depleted Gr-1(+) neutrophils in vivo, and demonstrated that neutrophils are required for ear swelling, the accepted metric for a CHS response. Depletion of IL-17-producing dermal V gamma 4(+) cells and neutralization of IL-17 in vivo, respectively, also led to a significantly reduced CHS response and diminished neutrophil infiltration. Our findings here suggest that dermal gamma delta T cells have an intermediate phenotype of T cell residence, and play an important role in primary CHS through producing IL-17 to promote neutrophil infiltration.

• 出版日期2017-1-12