Regulation of NKT Cells by Ly49: Analysis of Primary NKT Cells and Generation of NKT Cell Line

Maeda, Motoi; Lohwasser, Stefan; Yamamura, Takashi; Takei, Fumio

doi:10.4049/jimmunol.167.8.4180

Cited by 53 publications

(59 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The role for differential expression of Ly49 molecules on NKT cell subsets is unclear. Maeda et al (64), have shown that Ly49 molecules can suppress NKT cell activation and IFN-␥ production in response to ␣-GalCer, but they did not distinguish between different Ly49 molecules. Ly49G2 recognizes the H-2 d haplotype of MHC class I, which is absent in C57BL/6 mice.…”

Section: Discussionmentioning

confidence: 99%

Differential Chemokine Responses and Homing Patterns of Murine TCRαβ NKT Cell Subsets

Johnston

Kim

Soler

et al. 2003

The Journal of Immunology

159

139

View full text Add to dashboard Cite

NKT cells play important roles in the regulation of diverse immune responses. Therefore, chemokine receptor expression and chemotactic responses of murine TCRαβ NKT cells were examined to define their homing potential. Most NKT cells stained for the chemokine receptor CXCR3, while >90% of Vα14i-positive and ∼50% of Vα14i-negative NKT cells expressed CXCR6 via an enhanced green fluorescent protein reporter construct. CXCR4 expression was higher on Vα14i-negative than Vα14i-positive NKT cells. In spleen only, subsets of Vα14i-positive and -negative NKT cells also expressed CXCR5. NKT cell subsets migrated in response to ligands for the inflammatory chemokine receptors CXCR3 (monokine induced by IFN-γ/CXC ligand (CXCL)9) and CXCR6 (CXCL16), and regulatory chemokine receptors CCR7 (secondary lymphoid-tissue chemokine (SLC)/CC ligand (CCL)21), CXCR4 (stromal cell-derived factor-1/CXCL12), and CXCR5 (B cell-attracting chemokine-1/CXCL13); but not to ligands for other chemokine receptors. Two NKT cell subsets migrated in response to the lymphoid homing chemokine SLC/CCL21: CD4− Vα14i-negative NKT cells that were L-selectinhigh and enriched for expression of Ly49G2 (consistent with the phenotype of most NKT cells found in peripheral lymph nodes); and immature Vα14i-positive cells lacking NK1.1 and L-selectin. Mature NK1.1+ Vα14i-positive NKT cells did not migrate to SLC/CCL21. BCA-1/CXCL13, which mediates homing to B cell zones, elicited migration of Vα14i-positive and -negative NKT cells in the spleen. These cells were primarily CD4+ or CD4−CD8− and were enriched for Ly49C/I, but not Ly49G2. Low levels of chemotaxis to CXCL16 were only detected in Vα14i-positive NKT cell subsets. Our results identify subsets of NKT cells with distinct homing and localization patterns, suggesting that these populations play specialized roles in immunological processes in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential Chemokine Responses and Homing Patterns of Murine TCRαβ NKT Cell Subsets

Johnston

Kim

Soler

et al. 2003

The Journal of Immunology

159

139

View full text Add to dashboard Cite

show abstract

“…Although all Ly49 receptors were cloned from NK cells, expression of Ly49 is not restricted to NK cells but it is also detected in CD8 ϩ T (32) and NKT cells (33). It has been reported that Ly49-negative NKT cells can be stimulated with ␣-GalCer-pulsed DCs, whereas Ly49-positive NKT cells do not respond (34). Thus, we examined the expression of Ly49A, Ly49C/I, and Ly49G2 on NKT cells from LFA-1 ϩ/ϩ and LFA-1…”

Section: Activation Of Nkt Cells In Lfa-1 ϫ/ϫ Micementioning

confidence: 99%

Essential Role of LFA-1 in Activating Th2-Like Responses by α-Galactosylceramide-Activated NKT Cells

Matsumoto

Kubota

Omi

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

NKT cells produce large amounts of cytokines associated with both the Th1 (IFN-γ) and Th2 (IL-4) responses following stimulation of their invariant Vα14 Ag receptor. The role of adhesion molecules in the activation of NKT cells by the Vα14 ligand α-galactosylceramide (α-GalCer) remains unclear. To address this issue, LFA-1−/− (CD11a−/−) mice were used to investigate IL-4 and IFN-γ production by NKT cells following α-GalCer stimulation. Intriguingly, LFA-1−/− mice showed increased IL-4, IL-5, and IL-13 production and polarized Th2-type responses in response to α-GalCer in vitro and in vivo. Furthermore, the Th2-specific transcription factor GATA-3 was up-regulated in α-GalCer-activated NKT cells from LFA-1−/− mice. These results provide the first genetic evidence that the adhesion receptor LFA-1 has a crucial role in Th2-polarizing functions of NKT cells.

show abstract

“…Next we asked whether the deficiency of Bhlhe40 might affect the maturation status of iNKT cells. To answer this question, thymic iNKT cells from WT or Bhlhe40 −/− mice were used to compare the expression of Ly49 family members, which are described as being expressed on both developing and mature iNKT cells (15). Again, no major differences were observed in the expression of Ly49 family members between WT and Bhlhe40 −/− iNKT cells (Fig.…”

Section: Bhlhe40mentioning

confidence: 99%

Transcriptional regulator Bhlhe40 works as a cofactor of T-bet in the regulation of IFN-γ production iniNKT cells

Kanda

Yamanaka

Kojo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Invariant natural killer T (iNKT) cells are a subset of innate-like T cells that act as important mediators of immune responses. In particular, iNKT cells have the ability to immediately produce large amounts of IFN-γ upon activation and thus initiate immune responses in various pathological conditions. However, molecular mechanisms that control IFN-γ production in iNKT cells are not fully understood. Here, we report that basic helix-loop-helix transcription factor family, member e40 (Bhlhe40), is an important regulator for IFN-γ production in iNKT cells. Bhlhe40 is highly expressed in stage 3 thymic iNKT cells and iNKT1 subsets, and the level of Bhlhe40 mRNA expression is correlated with Ifng mRNA expression in the resting state. Although Bhlhe40-deficient mice show normal iNKT cell development, Bhlhe40-deficient iNKT cells show significant impairment of IFN-γ production and antitumor effects. Bhlhe40 alone shows no significant effects on Ifng promoter activities but contributes to enhance T-box transcription factor Tbx21 (T-bet)-mediated Ifng promoter activation. Chromatin immunoprecipitation analysis revealed that Bhlhe40 accumulates in the T-box region of the Ifng locus and contributes to histone H3-lysine 9 acetylation of the Ifng locus, which is impaired without T-bet conditions. These results indicate that Bhlhe40 works as a cofactor of T-bet for enhancing IFN-γ production in iNKT cells.

show abstract

Regulation of NKT Cells by Ly49: Analysis of Primary NKT Cells and Generation of NKT Cell Line

Cited by 53 publications

References 41 publications

Differential Chemokine Responses and Homing Patterns of Murine TCRαβ NKT Cell Subsets

Differential Chemokine Responses and Homing Patterns of Murine TCRαβ NKT Cell Subsets

Essential Role of LFA-1 in Activating Th2-Like Responses by α-Galactosylceramide-Activated NKT Cells

Transcriptional regulator Bhlhe40 works as a cofactor of T-bet in the regulation of IFN-γ production iniNKT cells

Contact Info

Product

Resources

About