The CD100 receptor interacts with its plexin B2 ligand to regulate epidermal γδ T cell function.
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.
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Deborah A
DA
Witherden
Megumi
M
Watanabe
Olivia
O
Garijo
Stephanie E
SE
Rieder
Gor
G
Sarkisyan
Shane J F
SJ
Cronin
Petra
P
Verdino
Ian A
IA
Wilson
Atsushi
A
Kumanogoh
Hitoshi
H
Kikutani
Luc
L
Teyton
Wolfgang H
WH
Fischer
Wendy L
WL
Havran
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D016466:CHO Cells; D002450:Cell Communication / Q000276:immunology; D048430:Cell Shape; D006224:Cricetinae; D004817:Epidermis / Q000276:immunology / Q000293:injuries; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D039961:Semaphorins / Q000276:immunology* / Q000378:metabolism; D020539:Sequence Analysis, Protein; D020349:Surface Plasmon Resonance; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014945:Wound Healing / Q000276:immunology
D051339:Actin Depolymerizing Factors; D015703:Antigens, CD; C093224:CD100 antigen; D009419:Nerve Tissue Proteins; C519231:Plxnb2 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D039961:Semaphorins; D048049:Extracellular Signal-Regulated MAP Kinases