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 block...
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| Veröffentlicht in: | Immunity (Cambridge, Mass.) Mass.), 2012-08, Vol.37 (2), p.314-325 |
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| creator | 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. |
| description | 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 |
| doi_str_mv | 10.1016/j.immuni.2012.05.026 |
| format | Article |
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► 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</description><identifier>ISSN: 1074-7613</identifier><identifier>EISSN: 1097-4180</identifier><identifier>DOI: 10.1016/j.immuni.2012.05.026</identifier><identifier>PMID: 22902232</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>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</subject><ispartof>Immunity (Cambridge, Mass.), 2012-08, Vol.37 (2), p.314-325</ispartof><rights>2012 Elsevier Inc.</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><rights>2012 Elsevier Inc. All rights reserved. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3786-d826d69e9806daaea6d95654019e257072f544e9d76dc52c246ac55fd76a2c213</citedby><cites>FETCH-LOGICAL-c3786-d826d69e9806daaea6d95654019e257072f544e9d76dc52c246ac55fd76a2c213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.immuni.2012.05.026$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22902232$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Witherden, Deborah A.</creatorcontrib><creatorcontrib>Watanabe, Megumi</creatorcontrib><creatorcontrib>Garijo, Olivia</creatorcontrib><creatorcontrib>Rieder, Stephanie E.</creatorcontrib><creatorcontrib>Sarkisyan, Gor</creatorcontrib><creatorcontrib>Cronin, Shane J.F.</creatorcontrib><creatorcontrib>Verdino, Petra</creatorcontrib><creatorcontrib>Wilson, Ian A.</creatorcontrib><creatorcontrib>Kumanogoh, Atsushi</creatorcontrib><creatorcontrib>Kikutani, Hitoshi</creatorcontrib><creatorcontrib>Teyton, Luc</creatorcontrib><creatorcontrib>Fischer, Wolfgang H.</creatorcontrib><creatorcontrib>Havran, Wendy L.</creatorcontrib><title>The CD100 Receptor Interacts with Its Plexin B2 Ligand to Regulate Epidermal γδ T Cell Function</title><title>Immunity (Cambridge, Mass.)</title><addtitle>Immunity</addtitle><description>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</description><subject>Actin Depolymerizing Factors - metabolism</subject><subject>Animals</subject><subject>Antigens, CD - immunology</subject><subject>Antigens, CD - metabolism</subject><subject>Cell Communication - immunology</subject><subject>Cell Shape</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Epidermis - immunology</subject><subject>Epidermis - injuries</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Keratinocytes - immunology</subject><subject>Keratinocytes - metabolism</subject><subject>Langerhans Cells - immunology</subject><subject>Langerhans Cells - metabolism</subject><subject>Lymphocyte Activation - immunology</subject><subject>Mass Spectrometry</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Nerve Tissue Proteins - immunology</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Phosphorylation</subject><subject>Protein Binding - immunology</subject><subject>Receptors, Antigen, T-Cell, gamma-delta - immunology</subject><subject>Receptors, Antigen, T-Cell, gamma-delta - metabolism</subject><subject>Semaphorins - immunology</subject><subject>Semaphorins - metabolism</subject><subject>Sequence Analysis, Protein</subject><subject>Surface Plasmon Resonance</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - metabolism</subject><subject>Wound Healing - immunology</subject><issn>1074-7613</issn><issn>1097-4180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFuEzEQhlcIREvhDRDykcsuY6_tzV6QILQQKRIVCmfL2JPE0a4dbG9pnwueo8-Eo5QCl55mRv7nH898VfWSQkOByje7xo3j5F3DgLIGRANMPqpOKfRdzekMHh_yjtedpO1J9SylHQDlooen1QljPTDWstNKr7ZI5h8oAPmCBvc5RLLwGaM2OZEfLm_JoiSXA147T94zsnQb7S3Joeg306AzkvO9sxhHPZDbn7e_yIrMcRjIxeRNdsE_r56s9ZDwxV08q75enK_mn-rl54-L-btlbdpuJms7Y9LKHvsZSKs1aml7IQUH2iMTHXRsLTjH3nbSGsEM41IbIdal1qWi7Vn19ui7n76NaA36HPWg9tGNOt6ooJ36_8W7rdqEK9XyFiTIYvD6ziCG7xOmrEaXTFlFewxTUhRaIVjHgBUpP0pNDClFXN-PoaAOdNROHemoAx0FQhU6pe3Vv1-8b_qD4-8OWA515TCqZBx6g9ZFNFnZ4B6e8BvkhaMC</recordid><startdate>20120824</startdate><enddate>20120824</enddate><creator>Witherden, Deborah A.</creator><creator>Watanabe, Megumi</creator><creator>Garijo, Olivia</creator><creator>Rieder, Stephanie E.</creator><creator>Sarkisyan, Gor</creator><creator>Cronin, Shane J.F.</creator><creator>Verdino, Petra</creator><creator>Wilson, Ian A.</creator><creator>Kumanogoh, Atsushi</creator><creator>Kikutani, Hitoshi</creator><creator>Teyton, Luc</creator><creator>Fischer, Wolfgang H.</creator><creator>Havran, Wendy L.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120824</creationdate><title>The CD100 Receptor Interacts with Its Plexin B2 Ligand to Regulate Epidermal γδ T Cell Function</title><author>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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3786-d826d69e9806daaea6d95654019e257072f544e9d76dc52c246ac55fd76a2c213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Actin Depolymerizing Factors - metabolism</topic><topic>Animals</topic><topic>Antigens, CD - immunology</topic><topic>Antigens, CD - metabolism</topic><topic>Cell Communication - immunology</topic><topic>Cell Shape</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Epidermis - immunology</topic><topic>Epidermis - injuries</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Keratinocytes - immunology</topic><topic>Keratinocytes - metabolism</topic><topic>Langerhans Cells - immunology</topic><topic>Langerhans Cells - metabolism</topic><topic>Lymphocyte Activation - immunology</topic><topic>Mass Spectrometry</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Nerve Tissue Proteins - immunology</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Phosphorylation</topic><topic>Protein Binding - immunology</topic><topic>Receptors, Antigen, T-Cell, gamma-delta - immunology</topic><topic>Receptors, Antigen, T-Cell, gamma-delta - metabolism</topic><topic>Semaphorins - immunology</topic><topic>Semaphorins - metabolism</topic><topic>Sequence Analysis, Protein</topic><topic>Surface Plasmon Resonance</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - metabolism</topic><topic>Wound Healing - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Witherden, Deborah A.</creatorcontrib><creatorcontrib>Watanabe, Megumi</creatorcontrib><creatorcontrib>Garijo, Olivia</creatorcontrib><creatorcontrib>Rieder, Stephanie E.</creatorcontrib><creatorcontrib>Sarkisyan, Gor</creatorcontrib><creatorcontrib>Cronin, Shane J.F.</creatorcontrib><creatorcontrib>Verdino, Petra</creatorcontrib><creatorcontrib>Wilson, Ian A.</creatorcontrib><creatorcontrib>Kumanogoh, Atsushi</creatorcontrib><creatorcontrib>Kikutani, Hitoshi</creatorcontrib><creatorcontrib>Teyton, Luc</creatorcontrib><creatorcontrib>Fischer, Wolfgang H.</creatorcontrib><creatorcontrib>Havran, Wendy L.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Immunity (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Witherden, Deborah A.</au><au>Watanabe, Megumi</au><au>Garijo, Olivia</au><au>Rieder, Stephanie E.</au><au>Sarkisyan, Gor</au><au>Cronin, Shane J.F.</au><au>Verdino, Petra</au><au>Wilson, Ian A.</au><au>Kumanogoh, Atsushi</au><au>Kikutani, Hitoshi</au><au>Teyton, Luc</au><au>Fischer, Wolfgang H.</au><au>Havran, Wendy L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The CD100 Receptor Interacts with Its Plexin B2 Ligand to Regulate Epidermal γδ T Cell Function</atitle><jtitle>Immunity (Cambridge, Mass.)</jtitle><addtitle>Immunity</addtitle><date>2012-08-24</date><risdate>2012</risdate><volume>37</volume><issue>2</issue><spage>314</spage><epage>325</epage><pages>314-325</pages><issn>1074-7613</issn><eissn>1097-4180</eissn><abstract>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</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22902232</pmid><doi>10.1016/j.immuni.2012.05.026</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Immunity (Cambridge, Mass.), 2012-08, Vol.37 (2), p.314-325 |
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| source | MEDLINE; Cell Press Free Archives; Access via ScienceDirect (Elsevier); EZB-FREE-00999 freely available EZB journals |
| 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 |
| title | The CD100 Receptor Interacts with Its Plexin B2 Ligand to Regulate Epidermal γδ T Cell Function |
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