Identification of a Novel Proinflammatory Human Skin-Homing Vγ9Vδ2 T Cell Subset with a Potential Role in Psoriasis

Abstract

γδ T cells mediate rapid tissue responses in murine skin and participate in cutaneous immune regulation including protection against cancer. The role of human γδ cells in cutaneous homeostasis and pathology is poorly characterized. In this study we show in vivo evidence that human blood contains a distinct subset of pro-inflammatory cutaneous lymphocyte antigen (CLA) and C-C chemokine receptor (CCR) 6 positive Vγ9Vδ2 T cells, which is rapidly recruited into perturbed human skin. Vγ9Vδ2 T cells produced an array of pro-inflammatory mediators including IL-17A and activated keratinocytes in a TNF-α and IFN-γ dependent manner. Examination of the common inflammatory skin disease psoriasis revealed a striking reduction of circulating Vγ9Vδ2 T cells in psoriasis patients compared to healthy controls and atopic dermatitis patients. Decreased numbers of circulating Vγ9Vδ2 T cells normalized after successful treatment with psoriasis-targeted therapy. Together with the increased presence of Vγ9Vδ2 T cells in psoriatic skin, this data indicates redistribution of Vγ9Vδ2 T cells from the blood to the skin compartment in psoriasis. In summary, we report a novel human pro-inflammatory γδ T cell involved in skin immune surveillance with immediate response characteristics and with potential clinical relevance in inflammatory skin disease.

Langerin neg conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice

“…In particular, dermis infiltrating γδ T-cell subsets as well as TCR neg RORγt + innate lymphocytes that rapidly produce IL-17/IL-22 upon stimulation with IL-23 and IL-1β, appear to be critical for the development of psoriasiform dermatitis in mice. In agreement, an increased frequency of Vγ9 + Vδ2 + T cells was described in human psoriatic skin (7). Despite accumulating evidence that activation of innate immune pathways plays a critical role in the initiation of psoriasis, it remains unclear how these pathways are triggered in vivo.…”

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

“…High frequency of γδ T cells is detected in psoriasiform dermal lesions in mice induced by IMQ, and these cells produce IL‐17 through stimulation with IL‐23,23 indicating the innate immune nature of the disease. γδ T cells, especially V γ 9 + V δ 2 + cells which can produce IL‐17, are also accumulated in the skin of patients with psoriasis 93. In this report, however, V γ 9 + V δ 2 + cells were activated to produce cytokines from keratinocytes by the specific antigen, suggesting that recognition of specific antigens may be important for the development of psoriasis.…”

Inflammation induces dermal Vγ4 + γδT17 memory-like cells that travel to distant skin and accelerate secondary IL-17–driven responses

“…We speculate that local skin or oral inflammation may result in expansion of IL-17-producing cells in responding LNs, which could then home to the skin and act to generalize cutaneous inflammation. In this regard, γδT cells capable of producing IL-17 have been identified in the blood and skin of patients with psoriasis (3,15,16). Whereas expanded Vγ4 + Vδ4 + γδT17 cells may preferentially migrate to skin given CLA expression, it is possible that they may be recruited to other inflamed tissues where they could aggravate disease.…”