Dendritic cell migration and antigen presentation are coordinated by the opposing functions of the tetraspanins CD82 and CD37

Eleanor L. Jones, Janet L. Wee, Maria C. Demaria, Jessica Blakeley, Po Ki Ho, Javier Vega-Ramos, Jose A. Villadangos, Annemiek B. Van Spriel, Michael J. Hickey, Gunther J. Hammerling, Mark D. Wright

Research output: Contribution to journalArticleResearchpeer-review

Abstract

This study supports a new concept where the opposing functions of the tetraspanins CD37 and CD82 may coordinate changes in migration and Ag presentation during dendritic cell (DC) activation. We have previously published that CD37 is downregulated upon monocyte-derived DC activation, promotes migration of both skin and bone marrow-derived dendritic cells (BMDCs), and restrains Ag presentation in splenic and BMDCs. In this article, we show that CD82, the closest phylogenetic relative to CD37, appears to have opposing functions. CD82 is upregulated upon activation of BMDCs and monocyte-derived DCs, restrains migration of skin and BMDCs, supports MHC class II maturation, and promotes stable interactions between T cells and splenic DCs or BMDCs. The underlying mechanism involves the rearrangement of the cytoskeleton via a differential activation of small GTPases. Both CD37-/ - And CD82-/-BMDCs lack cellular projections, but where CD37-/-BMDCs spread poorly on fibronectin, CD82-/-BMDCs are large and spread to a greater extent than wild-type BMDCs. At the molecular level, CD82 is a negative regulator of RhoA, whereas CD37 promotes activation of Rac-1; both tetraspanins negatively regulate Cdc42. Thus, this study identifies a key aspect of DC biology: an unactivated BMDC is CD37hiCD82lo, resulting in a highly motile cell with a limited ability to activate naive T cells. By contrast, a late activated BMDC is CD37loCD82hi, and thus has modified its migratory, cytoskeletal, and Ag presentation machinery to become a cell superbly adapted to activating naive T cells.

Original languageEnglish
Pages (from-to)978-987
Number of pages10
JournalJournal of Immunology
Volume196
Issue number3
DOIs
Publication statusPublished - 1 Feb 2016

Cite this

Jones, Eleanor L. ; Wee, Janet L. ; Demaria, Maria C. ; Blakeley, Jessica ; Ho, Po Ki ; Vega-Ramos, Javier ; Villadangos, Jose A. ; Van Spriel, Annemiek B. ; Hickey, Michael J. ; Hammerling, Gunther J. ; Wright, Mark D. / Dendritic cell migration and antigen presentation are coordinated by the opposing functions of the tetraspanins CD82 and CD37. In: Journal of Immunology. 2016 ; Vol. 196, No. 3. pp. 978-987.
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title = "Dendritic cell migration and antigen presentation are coordinated by the opposing functions of the tetraspanins CD82 and CD37",
abstract = "This study supports a new concept where the opposing functions of the tetraspanins CD37 and CD82 may coordinate changes in migration and Ag presentation during dendritic cell (DC) activation. We have previously published that CD37 is downregulated upon monocyte-derived DC activation, promotes migration of both skin and bone marrow-derived dendritic cells (BMDCs), and restrains Ag presentation in splenic and BMDCs. In this article, we show that CD82, the closest phylogenetic relative to CD37, appears to have opposing functions. CD82 is upregulated upon activation of BMDCs and monocyte-derived DCs, restrains migration of skin and BMDCs, supports MHC class II maturation, and promotes stable interactions between T cells and splenic DCs or BMDCs. The underlying mechanism involves the rearrangement of the cytoskeleton via a differential activation of small GTPases. Both CD37-/ - And CD82-/-BMDCs lack cellular projections, but where CD37-/-BMDCs spread poorly on fibronectin, CD82-/-BMDCs are large and spread to a greater extent than wild-type BMDCs. At the molecular level, CD82 is a negative regulator of RhoA, whereas CD37 promotes activation of Rac-1; both tetraspanins negatively regulate Cdc42. Thus, this study identifies a key aspect of DC biology: an unactivated BMDC is CD37hiCD82lo, resulting in a highly motile cell with a limited ability to activate naive T cells. By contrast, a late activated BMDC is CD37loCD82hi, and thus has modified its migratory, cytoskeletal, and Ag presentation machinery to become a cell superbly adapted to activating naive T cells.",
author = "Jones, {Eleanor L.} and Wee, {Janet L.} and Demaria, {Maria C.} and Jessica Blakeley and Ho, {Po Ki} and Javier Vega-Ramos and Villadangos, {Jose A.} and {Van Spriel}, {Annemiek B.} and Hickey, {Michael J.} and Hammerling, {Gunther J.} and Wright, {Mark D.}",
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Dendritic cell migration and antigen presentation are coordinated by the opposing functions of the tetraspanins CD82 and CD37. / Jones, Eleanor L.; Wee, Janet L.; Demaria, Maria C.; Blakeley, Jessica; Ho, Po Ki; Vega-Ramos, Javier; Villadangos, Jose A.; Van Spriel, Annemiek B.; Hickey, Michael J.; Hammerling, Gunther J.; Wright, Mark D.

In: Journal of Immunology, Vol. 196, No. 3, 01.02.2016, p. 978-987.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Jones, Eleanor L.

AU - Wee, Janet L.

AU - Demaria, Maria C.

AU - Blakeley, Jessica

AU - Ho, Po Ki

AU - Vega-Ramos, Javier

AU - Villadangos, Jose A.

AU - Van Spriel, Annemiek B.

AU - Hickey, Michael J.

AU - Hammerling, Gunther J.

AU - Wright, Mark D.

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