Role of Gamma Delta T-Cells in Lymphedema-Related Infections
Adana-Christine Campbell*, Kevin Kuonqui, Stav Brown, Ananta Sarker, Babak Mehrara
Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
Background: Recurrent skin infections are a common problem for patients with secondary lymphedema (LE). Between 2012-2017, 92% of the LE-related hospitalizations in the US were for cellulitis. However, the cellular mechanisms that lead to an increased risk of infections with secondary LE remain unknown. Previous studies have shown that dermal IL-17 + γδ T-cells are a major regulator of cellulitis in other inflammatory skin conditions such as atopic dermatitis. The purpose of this study was to determine if secondary LE also results in disturbances in IL-17 production and changes in γδ T-cell populations.
Methods: Matched, full-thickness skin biopsies were obtained from the normal and LE limb of 10 patients with unilateral upper extremity LE. Half of our patients had a history of recurrent cellulitis; the remaining 5 patients had a history of LE without infections. The number of dermal IL-17 + CD4+ T cells and dermal IL-17 + γδ T-cell subsets in the normal and LE arm were assessed by immunohistochemistry (IHC) and Immunofluorescence (IF). We also analyzed IL17 expression and γδ T-cells in a mouse model of LE using PCR and Flow cytometry.
Results: In contrast to IL-17 + CD4+ cells, patients with a history of infections had a significant increase in the number of IL-17+ γδ T-cells (p=0.046) in their LE skin biopsies. In the mouse LE model, we found that LE resulted in an increase in the number of IL-17+ γδ T-cells and that application of Staph epidermidis further increased infiltration of these cells (p=0.0171). Similarly, IL-17 mRNA was increased on Q-PCR in the S. epidermidis treated mice compared to untreated controls.
Conclusions: Our findings suggest that IL-17+ γδ T-cells may play a role in LE-induced skin infections. This finding is consistent with previous studies in other inflammatory skin disorders demonstrating that IL-17+ γδ T-cells impair skin barrier function suggesting that a similar process may contribute to the risk of infections in LE. Future studies will analyze skin barrier function and correlate these changes to the risk of developing cellulitis
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