Regulation of the actin cytoskeleton by rho kinase controls antigen presentation by CD1d

Richard M. Gallo, Masood A. Khan, Jianjian Shi, Reuben Kapur, Lei Wei, Jennifer C. Bailey, Jianyun Liu, Randy Brutkiewicz

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

CD1d molecules are MHC class I-like molecules that present lipid Ags to NKT cells. Although we have previously shown that several different cell signaling molecules can play a role in the control of Ag presentation by CD1d, a defined mechanism by which a cell signaling pathway regulates CD1d function has been unclear. In the current study, we have found that the Rho kinases, Rho-associated, coiled-coil containing protein kinase (ROCK)1 and ROCK2, negatively regulate both human and mouse CD1d-mediated Ag presentation. Inhibition of ROCK pharmacologically, through specific ROCK1 and ROCK2 short hairpin RNA, or by using dendritic cells generated from ROCK1-deficient mice all resulted in enhanced CD1d-mediated Ag presentation compared with controls. ROCK regulates the actin cytoskeleton by phosphorylating LIM kinase, which, in turn, phosphorylates cofilin, prohibiting actin fiber depolymerization. Treatment of APCs with the actin filament depolymerizing agent, cytochalasin D, as well as knockdown of LIM kinase by short hairpin RNA, resulted in enhanced Ag presentation to NKT cells by CD1d, consistent with our ROCK inhibition data. Therefore, our overall results reveal a model whereby CD1d-mediated Ag presentation is negatively regulated by ROCK via its effects on the actin cytoskeleton.

Original languageEnglish
Pages (from-to)1689-1698
Number of pages10
JournalJournal of Immunology
Volume189
Issue number4
DOIs
StatePublished - Aug 15 2012

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rho-Associated Kinases
Antigen Presentation
Lim Kinases
Actin Cytoskeleton
Natural Killer T-Cells
Small Interfering RNA
CD1d Antigen
Actin Depolymerizing Factors
Cytochalasin D
Dendritic Cells
Actins
Lipids

ASJC Scopus subject areas

  • Immunology

Cite this

Regulation of the actin cytoskeleton by rho kinase controls antigen presentation by CD1d. / Gallo, Richard M.; Khan, Masood A.; Shi, Jianjian; Kapur, Reuben; Wei, Lei; Bailey, Jennifer C.; Liu, Jianyun; Brutkiewicz, Randy.

In: Journal of Immunology, Vol. 189, No. 4, 15.08.2012, p. 1689-1698.

Research output: Contribution to journalArticle

Gallo, Richard M. ; Khan, Masood A. ; Shi, Jianjian ; Kapur, Reuben ; Wei, Lei ; Bailey, Jennifer C. ; Liu, Jianyun ; Brutkiewicz, Randy. / Regulation of the actin cytoskeleton by rho kinase controls antigen presentation by CD1d. In: Journal of Immunology. 2012 ; Vol. 189, No. 4. pp. 1689-1698.
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