The CD100 Receptor Interacts with Its Plexin B2 Ligand to Regulate Epidermal γδ T Cell Function

• Published in: Immunity (Cambridge, Mass.) Mass.), 2012-08, Vol.37 (2), p.314-325
• Main Authors: Witherden, Deborah A., Watanabe, Megumi, Garijo, Olivia, Rieder, Stephanie E., Sarkisyan, Gor, Cronin, Shane J.F., Verdino, Petra, Wilson, Ian A., Kumanogoh, Atsushi, Kikutani, Hitoshi, Teyton, Luc, Fischer, Wolfgang H., Havran, Wendy L.
• Format: Article
• Language: English
• Subjects: Actin Depolymerizing Factors - metabolism; Animals; Antigens, CD - immunology; Antigens, CD - metabolism; Cell Communication - immunology; Cell Shape; CHO Cells; Cricetinae; Epidermis - immunology; Epidermis - injuries; Extracellular Signal-Regulated MAP Kinases - metabolism; HEK293 Cells; Humans; Keratinocytes - immunology; Keratinocytes - metabolism; Langerhans Cells - immunology; Langerhans Cells - metabolism; Lymphocyte Activation - immunology; Mass Spectrometry; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins - immunology; Nerve Tissue Proteins - metabolism; Phosphorylation; Protein Binding - immunology; Receptors, Antigen, T-Cell, gamma-delta - immunology; Receptors, Antigen, T-Cell, gamma-delta - metabolism; Semaphorins - immunology; Semaphorins - metabolism; Sequence Analysis, Protein; Surface Plasmon Resonance; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Wound Healing - immunology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2012.05.026

γδ T cells respond rapidly to keratinocyte damage, providing essential contributions to the skin wound healing process. The molecular interactions regulating their response are unknown. Here, we identify a role for interaction of plexin B2 with the CD100 receptor in epithelial repair. In vitro blocking of plexin B2 or CD100 inhibited γδ T cell activation. Furthermore, CD100 deficiency in vivo resulted in delayed repair of cutaneous wounds due to a disrupted γδ T cell response to keratinocyte damage. Ligation of CD100 in γδ T cells induced cellular rounding via signals through ERK kinase and cofilin. Defects in this rounding process were evident in the absence of CD100-mediated signals, thereby providing a mechanistic explanation for the defective wound healing in CD100-deficient animals. The discovery of immune functions for plexin B2 and CD100 provides insight into the complex cell-cell interactions between epithelial resident γδ T cells and the neighboring cells they support. ► Plexin B2 is a functional ligand for CD100 in mouse skin ► Plexin B2-CD100 interaction is required for epidermal γδ T cell activation ► CD100 ligation induces cellular rounding ► Plexin B2-CD100 interaction delivers signals through ERK and cofilin