Interaction of CD99 with Its Paralog CD99L2 Positively Regulates CD99L2 Trafficking to Cell Surfaces

Nam, Giri; Lee, Youngkwan; Lee, Hye Yeong; Jung, Min Ho; Araki, Masatake; Araki, Kimi; Lee, Seungbok; Lee, Im Soon; Choi, Eun Young

doi:10.4049/jimmunol.1203062

Cited by 8 publications

(6 citation statements)

References 44 publications

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“…It is known that PILR family members interact with CD99 ( Kogure et al, 2011 ; Lee et al, 2012 ; Nam et al, 2013 ; Sun et al, 2012 ; Tabata et al, 2008 ). As we have reported before, CD99 activation with monoclonal antibody recruited SHP2 and allowed it to dephosphorylate FAK at Y397 to regulate the FA complex, resulting in a decrease in β1 integrin activity ( Lee et al, 2012 ; 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Paired Ig-Like Type 2 Receptor-Derived Agonist Ligands Ameliorate Inflammatory Reactions by Downregulating β1 Integrin Activity

Lee¹,

Lim²,

Yoo³

et al. 2016

Molecules and Cells

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The paired immunoglobulin-like type 2 receptor (PILR) family consists of two functionally opposite members, inhibitory PILRα and activating PILRβ receptors. PILRs are widely expressed in various immune cells and interact with their ligands, especially CD99 expressed on activated T cells, to participate in immune responses. Here we investigated whether PILR-derived agonists inhibit β1 integrin activity as ligands for CD99. PILR-derived peptides as well as PILR-Fc fusion proteins prevented cell adhesion to fibronectin through the regulation of β1 integrin activity. Especially, PILRpep3, a representative 3-mer peptide covering the conserved motifs of the PILR extracellular domain, prevented the clustering and activation of β1 integrin by dephosphorylating FAK and vinculin, which are major components of focal adhesion. In addition, PILRpep3 inhibited transendothelial migration of monocytes as well as endothelial cell tube formation. Furthermore, upon intraperitoneal injection of PILRpep3 into mice with collagen-induced arthritis, the inflammatory response of rheumatoid arthritis was strongly suppressed. Taken together, these results suggest that PILR-derived agonist ligands may prevent the inflammatory reactions of rheumatoid arthritis by activating CD99.

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Section: Discussionmentioning

confidence: 99%

Paired Ig-Like Type 2 Receptor-Derived Agonist Ligands Ameliorate Inflammatory Reactions by Downregulating β1 Integrin Activity

Lee¹,

Lim²,

Yoo³

et al. 2016

Molecules and Cells

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“…CD99 does not increase to compensate for absence of CD99L2. A recent paper by Nam et al (Nam et al, 2013) showed that in mouse cells CD99 and CD99L2 interact via their cytoplasmic domains during their biosynthesis. CD99 helps CD99L2 get to the cell surface, and levels of CD99L2 were decreased in cells lacking CD99.…”

Section: Discussionmentioning

confidence: 99%

CD99-like 2 (CD99L2)-deficient mice are defective in the acute inflammatory response

Rutledge

Weber

Winger

et al. 2015

Experimental and Molecular Pathology

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CD99-Like 2 (CD99L2) is a Type I glycoprotein expressed on leukocytes and endothelial cells as well as other cell types. It is related to CD99, although it shows only 38% sequence identity. CD99L2 has been shown to play a role in leukocyte extravasation in mice under various inflammatory conditions using anti-CD99L2 antibodies and, in one case by targeted deletion of CD99L2. We report here studies on an independently made CD99L2 “knockout mouse” that extend our knowledge of the role of CD99L2 in inflammation. CD99L2 deficiency did not affect the total or relative numbers of circulating leukocyte subsets, red blood cells, or platelets. Neither did CD99L2 deficiency affect the expression of ICAM-1, PECAM, or CD99 on endothelial cells. Mice lacking CD99L2 had a defective inflammatory response in the thioglycollate peritonitis model with a greater than 80% block in neutrophil infiltration and a nearly complete block in monocyte emigration into the peritoneal cavity measured 16 hours after the inflammatory challenge. The mice will be a useful resource to study the role of CD99L2 in various acute and chronic inflammatory diseases.

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“…CD99 facilitates TEM through homophilic interactions between the two cell types [108]. Similarly, CD99L2 has been reported to function through homophilic interactions but it may have another unidentified ligand [109–111]. Disruption of CD99 and CD99L2 interactions using function blocking antibodies or genetic knock out (in the case of CD99L2) impairs leukocyte extravasation in vitro and in vivo.…”

Section: The Molecules Involved On the Endothelial Cellmentioning

confidence: 99%

“…Interestingly though, in a study using the mouse homologues of CD99 and CD99L2, Nam and coworkers showed that the two molecules interact with each other heterophilically through their cytoplasmic tails [111]. Through this interaction CD99 appears to facilitate the trafficking of CD99L2 to the plasma membrane.…”

Section: The Molecules Involved On the Endothelial Cellmentioning

confidence: 99%

Neutrophil and monocyte recruitment by PECAM, CD99, and other molecules via the LBRC

Sullivan

Müller

2013

Semin Immunopathol

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The recruitment of specific leukocyte subtypes to the site of tissue injury is the cornerstone of inflammation and disease progression. This process has become an intense area of research because it presents several possible steps against which disease-specific therapies could be targeted. Leukocytes are recruited out of the blood stream by a series of events that includes their capture, rolling, activation, and migration along the endothelium. In the last step, the leukocytes squeeze between adjacent endothelial cells to gain access to the inflamed tissue through a process referred to as transendothelial migration (TEM). Although many of the molecules, such as PECAM and CD99, that regulate these sequential steps have been identified, much less is understood regarding how they work together to coordinate the complex intercellular communications and dramatic shape changes that take place between the endothelial cells and leukocytes. Several of the endothelial cell proteins that function in TEM are localized to the Lateral Border Recycling Compartment (LBRC), an interconnected reticulum of membrane that recycles selectively to the endothelial borders. The recruitment of the LBRC to surround the migrating leukocyte is required for efficient TEM. This review will focus on the proteins and mechanisms that mediate TEM and specifically how the LBRC functions in the context of these molecular interactions and membrane movements.

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Interaction of CD99 with Its Paralog CD99L2 Positively Regulates CD99L2 Trafficking to Cell Surfaces

Cited by 8 publications

References 44 publications

Paired Ig-Like Type 2 Receptor-Derived Agonist Ligands Ameliorate Inflammatory Reactions by Downregulating β1 Integrin Activity

Paired Ig-Like Type 2 Receptor-Derived Agonist Ligands Ameliorate Inflammatory Reactions by Downregulating β1 Integrin Activity

CD99-like 2 (CD99L2)-deficient mice are defective in the acute inflammatory response

Neutrophil and monocyte recruitment by PECAM, CD99, and other molecules via the LBRC

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