LB1023 Deletion of bardet biedl syndrome 1 (BBS1) gene in T cells impairs wound healing in mice

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Primary cilia play an important role in cell directional migration and tissue repair. Ciliary function depends on several proteins including the BBSome, a complex of eight conserved Bardet-Biedl syndrome (BBS) proteins, such as BBS1, which transport cargos to and from cilia. The immune synapse (IS), the nano-scale gap between T cells and antigen presenting cells, in non-ciliated T cells is functionally homologous to the primary cilium. During the formation of the IS, the BBSome appears to be critical for centrosome translocation toward the IS interface within T cells. Data from our lab demonstrate that BBS1 hypomorphic mice (containing a systemic homozygous knock-in missense mutation) characteristically exhibit impaired cilia function, altered fibroblast function, and reduced wound healing/tissue repair. The skin is residence for most lymphocytes in the body. To investigate the role of BBS1 in T cells in wound healing, we generated a novel transgenic mouse model in which the BBS1 gene was conditionally deleted in T cells. For in vivo wound healing, 2 mm full-thickness punch biopsy was performed on the shaved backs of 9 to 11 weeks old male and female T-BBS1-/- mice and their wild-type littermate controls and assessed for rate of wound closure by secondary intention between day 0 and day 7. The wounds formed fibrin clots at similar times in both T-BBS1-/- and littermate controls. However, male T-BBS1-/- mice demonstrated significantly delayed wound healing at day 7 compared to controls (4.061±1.79%, p=0.0342, n=10-12/group). The female mice show a trend toward reduced would healing at 7 days as well. These results demonstrate that BBS1 plays an important role in T cell mediated skin repair and that this effect may be sex specific.