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Functional Characterization of Skin Dendritic Cell Subpopulations in Immune Response and Modulation of Vascularized Composite Allotransplantation (VCA)

Wensheng Zhang, Chiaki Komatsu, Jiaqing Wu, Firuz Feturi, Jingjing Li, Maxine Miller, Alicia Mathers, Angus Thomson, Vijay Gorantla, Kia Washington, Mario Solari
Department of Plastic Surgery, University of Pittsburgh
2018-02-01

Presenter: Wensheng Zhang

Affidavit:
I certify that the material proposed foI certify material I I certify that the material proposed in this abstract has not been published in any scientific journal or previously presented at a major meeting.

Director Name: Mario Solari

Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction

INTRODUCTION: Skin dendritic cells (DC) are gaining prominence as one of the principal players orchestrating immunity and tolerance. In our earlier work, we demonstrated the dynamics and the associated immune response profiles in VCA. In this study, we further evaluated the function of skin-migrated/resident DC subsets on regulating the T-cell immune response and characterized their changes in VCA under topical immunosuppression.

METHODS: LEW rats received hind-limb transplants from BN rats and were treated with daily topical FK506 ointment on allografts. Skin-resident DC from limb allografts were isolated and quantified at day 8 post-transplantation. Skin-migrated DC were harvested in vitro after limb skin was cultured for 72h under a stimulation condition and were characterized for their functional specialization in a mixed lymphocyte reaction (MLR).

RESULTS: Skin-resident dermal DC (DDC) declined in number while Langerhans cells (LC) slightly elevated after topical FK506 treatment. Skin-migrated mature DC and LC were decreased with mildly enhanced DDC in FK506-treated skin explant cultures. In MLR, skin-migrated DC exerted a suppressive action on effector T-cells (Teff) proliferation and synergized with regulator T-cells (Treg) in controlling T-cell responses, paralleling the induction of Foxp3+ Treg conversion. In contrast, skin-resident DC exhibited immunogenic function, accompanied by downmodulating Foxp3 and upmodulating IL-17 expression in T cells.

CONCLUSIONS: Skin-migrated DC act on the VCA immune response through differential modulation of Treg/Th17 balance. Alteration of migration and maturation of skin DC subsets in VCA is effected by short-term topical immunosuppression. Functional determination of skin DC will allow for the development of targeted therapies.

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