Type II Natural Killer T Cells that Recognize Sterol Carrier Protein 2 Are Implicated in Vascular Inflammation in the Rat Model of Systemic Connective Tissue Diseases

Nishioka, Yusuke; Yamaguchi, M; Kawakami, Ai; Munehiro, Maya; Masuda, Sakiko; Tomaru, Utano; Ishizu, Akihiro

doi:10.1016/j.ajpath.2016.09.014

Cited by 6 publications

(10 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a subsequent study, a more potent phosphatidylglycerol antigen from Listeria monocytogenes was identified that had a structure distinct from previously identified mammalian or microbial variants, as it contains short, fully saturated anteiso fatty acid lipid tails (32). Type II NKT cells may not only recognize lipid antigens but a recent study suggests that they also can recognize hydrophobic peptides presented on CD1d (33, 34). A report by Nishioka et al found that a rat type II NKT cell clone, reactive to vascular endothelial cells, could recognize a CD1d-presented hydrophobic peptide derived from sterol carrier protein 2, a protein implicated in intracellular lipid transfer.…”

Section: Antigens For Type II Nkt Cellsmentioning

confidence: 99%

Type II NKT Cells: An Elusive Population With Immunoregulatory Properties

2018

View full text Add to dashboard Cite

Natural killer T (NKT) cells are unique unconventional T cells that are reactive to lipid antigens presented on the non-polymorphic major histocompatibility class (MHC) I-like molecule CD1d. They have characteristics of both innate and adaptive immune cells, and have potent immunoregulatory roles in tumor immunity, autoimmunity, and infectious diseases. Based on their T cell receptor (TCR) expression, NKT cells are divided into two subsets, type I NKT cells with an invariant TCRα-chain (Vα24 in humans, Vα14 in mice) and type II NKT cells with diverse TCRs. While type I NKT cells are well-studied, knowledge about type II NKT cells is still limited, and it is to date only possible to identify subsets of this population. However, recent advances have shown that both type I and type II NKT cells play important roles in many inflammatory situations, and can sometimes regulate the functions of each other. Type II NKT cells can be both protective and pathogenic. Here, we review current knowledge on type II NKT cells and their functions in different disease settings and how these cells can influence immunological outcomes.

show abstract

Section: Antigens For Type II Nkt Cellsmentioning

confidence: 99%

Type II NKT Cells: An Elusive Population With Immunoregulatory Properties

2018

View full text Add to dashboard Cite

show abstract

“…In our earlier study, we identified rSCP2 518-532 , FFQGKLKIAGNMGLA, as the epitope, which was recognized by one of rat CD1d-restricted type II NKT cells (10). In this study, we attempted to detect human CD1d-restricted type II NKT cells in peripheral blood using hSCP2 518-532 , FFQGPLKITGNMGLA, the human counterpart of rSCP2 518-532, together with a CD1d tetramer in flow cytometry.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the association of impaired CD1drestricted type II NKT cells with inflammatory diseases has also been reported. Recently, we identified P 518-532 of rat sterol carrier protein 2 (rSCP2 518-532 ), FFQGKLKIAGNMGLA, as the epitope, which was recognized by one such CD1d-restricted type II NKT cell (10). In addition, we have shown that proinflammatory autologous vascular endothelial cell-reactive CD1d-restricted type II NKT cells were involved in the development of vasculitis in rats (9).…”

mentioning

confidence: 99%

“…In addition, we have shown that proinflammatory autologous vascular endothelial cell-reactive CD1d-restricted type II NKT cells were involved in the development of vasculitis in rats (9). Recently, we identified P 518-532 of rat sterol carrier protein 2 (rSCP2 518-532 ), FFQGKLKIAGNMGLA, as the epitope, which was recognized by one such CD1d-restricted type II NKT cell (10).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Detection of Autoreactive Type II NKT Cells: A Pilot Study of Comparison Between Healthy Individuals and Patients with Vasculitis

et al. 2018

Self Cite

View full text Add to dashboard Cite

NKT cells are defined as T cells that recognize hydrophobic antigens presented by class I MHC-like molecules, including CD1d. Among CD1d-restricted NKT cells, type I and type II subsets have been noted. CD1d-restricted type I NKT cells are regarded as proinflammatory cells in general. On the contrary, accumulated evidence has demonstrated an anti-inflammatory property of CD1d-restricted type II NKT cells. In our earlier study using a rat model with vasculitis, we demonstrated the pro-inflammatory function of CD1d-restricted type II NKT cells and identified that one such cell recognized P 518-532 of rat sterol carrier protein 2 (rSCP2 518-532 ), which appeared on vascular endothelial cells presented by CD1d. Based on this evidence, we attempted to detect human CD1d-restricted type II NKT cells in peripheral blood using hSCP2 518-532 , the human counterpart of rSCP2 518-532, together with a CD1d tetramer in flow cytometry. First, we determined the binding of hSCP2 518-532 to CD1d. Next, we detected CD3-positive hSCP2 518-532 -loaded CD1d (hSCP2 518-532 /CD1d) tetramer-binding cells in peripheral blood of healthy donors. The abundance of TGF-β-producing cells rather than TNF-α-producing cells in CD3-positive hSCP2 518-532 /CD1d tetramer-binding cells suggests the anti-inflammatory property of SCP2-loaded CD1d (SCP2/CD1d) tetramer-binding type II NKT cells in healthy individuals. Furthermore, we compared cytokine profile between healthy individuals and patients with vasculitis in a pilot study. Interestingly, the percentage of TGF-β-producing cells in SCP2/CD1d tetramerbinding type II NKT cells in vasculitic patients was significantly lower than that in healthy controls despite the greater number of these cells. Although further studies to clarify the mechanism and significance of this phenomenon are needed, SCP2/CD1d tetramer-binding type II NKT cells in peripheral blood should be examined in more detail to understand the pathophysiology of vasculitides in humans.

show abstract

“…Although they did not declare the subtype of type II collagen-reactive CD1d-restricted NKT cells in the paper, it appears to be a type II phenotype in terms of the antigen property. More recently, our group demonstrated that the hydrophobic peptide derived from sterol carrier protein 2 (SCP2), an intracellular lipid transporter, could be presented by CD1d and then recognized by CD1d-restricted type II NKT cells ( 25 ). Girardi et al conducted X-ray analyzes of binding formation of CD1d and peptide antigens ( 26 ).…”

Section: Antigens Recognized By Cd1d-restricted Type II Nkt Cellsmentioning

confidence: 99%

CD1d-Restricted Type II NKT Cells Reactive With Endogenous Hydrophobic Peptides

et al. 2018

Self Cite

View full text Add to dashboard Cite

NKT cells belong to a distinct subset of T cells that recognize hydrophobic antigens presented by major histocompatibility complex class I-like molecules, such as CD1d. Because NKT cells stimulated by antigens can activate or suppress other immunocompetent cells through an immediate production of a large amount of cytokines, they are regarded as immunological modulators. CD1d-restricted NKT cells are classified into two subsets, namely, type I and type II. CD1d-restricted type I NKT cells express invariant T cell receptors (TCRs) and react with lipid antigens, including the marine sponge-derived glycolipid α-galactosylceramide. On the contrary, CD1d-restricted type II NKT cells recognize a wide variety of antigens, including glycolipids, phospholipids, and hydrophobic peptides, by their diverse TCRs. In this review, we focus particularly on CD1d-restricted type II NKT cells that recognize endogenous hydrophobic peptides presented by CD1d. Previous studies have demonstrated that CD1d-restricted type I NKT cells usually act as pro-inflammatory cells but sometimes behave as anti-inflammatory cells. It has been also demonstrated that CD1d-restricted type II NKT cells play opposite roles to CD1d-restricted type I NKT cells; thus, they function as anti-inflammatory or pro-inflammatory cells depending on the situation. In line with this, CD1d-restricted type II NKT cells that recognize type II collagen peptide have been demonstrated to act as anti-inflammatory cells in diverse inflammation-induction models in mice, whereas pro-inflammatory CD1d-restricted type II NKT cells reactive with sterol carrier protein 2 peptide have been demonstrated to be involved in the development of small vessel vasculitis in rats.

show abstract

Type II Natural Killer T Cells that Recognize Sterol Carrier Protein 2 Are Implicated in Vascular Inflammation in the Rat Model of Systemic Connective Tissue Diseases

Cited by 6 publications

References 30 publications

Type II NKT Cells: An Elusive Population With Immunoregulatory Properties

Type II NKT Cells: An Elusive Population With Immunoregulatory Properties

Detection of Autoreactive Type II NKT Cells: A Pilot Study of Comparison Between Healthy Individuals and Patients with Vasculitis

CD1d-Restricted Type II NKT Cells Reactive With Endogenous Hydrophobic Peptides

Contact Info

Product

Resources

About