HP-1Î³ Controls High-Affinity Antibody Response to T-Dependent Antigens

Ha, Ngoc T; Pham, Duc Hung; Shahsafaei, Aliakbar; Naruse, Chie; Asano, Masahide; Thai, To‐Ha

doi:10.3389/fimmu.2014.00271

Cited by 8 publications

(8 citation statements)

References 30 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, we showed that in C57BL/6 mice, haploinsufficiency of Cbx3 /HP1γ impairs the lymphoid-tissue germinal center (GC) reaction and high-affinity antibody response against a thymus (T)-dependent antigen (Ag) conjugated to chicken gamma globulin (NP-CGG) 15 . The effects were CD8 + -T-cell-intrinsic.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Cbx3/HP1γ deficiency confers enhanced tumor-killing capacity on CD8+ T cells

Sun

Pham

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Cbx3/HP1γ is a histone reader whose function in the immune system is not completely understood. Here, we demonstrate that in CD8+ T cells, Cbx3/HP1γ insufficiency leads to chromatin remodeling accompanied by enhanced Prf1, Gzmb and Ifng expression. In tumors obtained from Cbx3/HP1γ-insufficient mice or wild type mice treated with Cbx3/HP1γ-insufficient CD8+ T cells, there is an increase of CD8+ effector T cells expressing the stimulatory receptor Klrk1/NKG2D, a decrease in CD4+ CD25+ FOXP3+ regulatory T cells (Treg cells) as well as CD25+ CD4+ T cells expressing the inhibitory receptor CTLA4. Together these changes in the tumor immune environment may have mitigated tumor burden in Cbx3/HP1γ-insufficient mice or wild type mice treated with Cbx3/HP1γ-insufficient CD8+ T cells. These findings suggest that targeting Cbx3/HP1γ can represent a rational therapeutic approach to control growth of solid tumors.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Homozygous germline deletion of Cbx3 /HP1γ in mice causes embryonic lethality 13 14 . Previously we have shown that Cbx3 /HP1γ haploinsufficiency is sufficient to regulate the high-affinity antibody response to protein antigens 15 . However, it has not been determined how Cbx3 /HP1γ does so.…”

mentioning

confidence: 98%

Cbx3/HP1γ deficiency confers enhanced tumor-killing capacity on CD8+ T cells

Sun

Pham

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our recent studies suggest that such an approach is attainable. We show that by targeting the histone reader Cbx3 /HP1γ, we can enhance the tumor killing capacity of effector CD8 + T cells ( 69 , 70 ). As a result, adoptive transfer of Cbx3 /HP1γ-deficient CD8 + effector T cells alone into wild type (wt) tumor-bearing mice greatly reduces NB growth.…”

Section: Adoptive T-cell Therapy (Act)mentioning

confidence: 92%

The State of Cellular Adoptive Immunotherapy for Neuroblastoma and Other Pediatric Solid Tumors

Thai

2017

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Research on adult cancer immunotherapy is proceeding at a rapid pace resulting in an impressive success rate exemplified by a few high profile cases. However, this momentum is not readily extended to pediatric immunotherapy, and it is not for lack of trying. Though reasons for the slower advance are not apparent, some issues can be raised. Pediatric cancer patients represent a distinct demographic group whose immune system is inherently different from that of mature adults. Treating pediatric patients with immunotherapy designed for adults may not yield objective clinical responses. Here, we will present an update on adoptive T-cell and natural killer-cell therapies for neuroblastoma and other childhood solid tumors. Additionally, we will delineate key differences between human fetal/neonatal and adult immune systems. We hope this will generate interests leading to the discussion of potential future directions for improving adoptive cancer immunotherapy for children.

show abstract

“…The mammalian HP1 family consists of three members, HP1α, HP1β, and HP1γ, coded by Cbx5 , Cbx1, and Cbx3 genes, respectively . Their localization in the cell nucleus is different despite their high amino acid sequence similarity suggesting that each HP1 has unique functions as seen in gene knockout studies . In neural tissues, HP1β and HP1γ are involved in neural development.…”

Section: Introductionmentioning

confidence: 99%

“…15 Their localization in the cell nucleus is different despite their high amino acid sequence similarity 28,29 suggesting that each HP1 has unique functions as seen in gene knockout studies. [30][31][32][33][34][35] In neural tissues, HP1β and HP1γ are involved in neural development. Mutations in HP1β cause defects in proliferation of nerve cell precursors accompanied by increased genome instability, reflecting the function of HP1β to stabilize heterochromatin.…”

Section: Introductionmentioning

confidence: 99%

Heterochromatin protein 1γ deficiency decreases histone H3K27 methylation in mouse neurosphere neuronal genes

et al. 2020

Self Cite

View full text Add to dashboard Cite

Heterochromatin protein (HP) 1γ, a component of heterochromatin in eukaryotes, is involved in H3K9 methylation. Although HP1γ is expressed strongly in neural tissues and neural stem cells, its functions are unclear. To elucidate the roles of HP1γ, we analyzed HP1γ ‐deficient (HP1γ KO) mouse embryonic neurospheres and determined that HP1γ KO neurospheres tended to differentiate after quaternary culture. Several genes normally expressed in neuronal cells were upregulated in HP1γ KO undifferentiated neurospheres, but not in the wild type (WT). Compared to that in the control neurospheres, the occupancy of H3K27me3 was lower around the transcription start sites (TSSs) of these genes in HP1γ KO neurospheres, while H3K9me2/3, H3K4me3, and H3K27ac amounts remained unchanged. Moreover, amounts of the H3K27me2/3 demethylases, UTX, and JMJD3, were increased around the TSSs of these genes. Treatment with GSK‐J4, an inhibitor of H3K27 demethylases, decreased the expression of genes upregulated in HP1γ KO neurospheres, along with an increase of H3K27me3 amounts. Therefore, in murine neurospheres, HP1γ protected the promoter sites of differentiated cell‐specific genes against H3K27 demethylases to repress the expression of these genes. A better understanding of central cellular processes such as histone methylation will help elucidate critical events such as cell‐specific gene expression, epigenetics, and differentiation.

show abstract

HP-1Î³ Controls High-Affinity Antibody Response to T-Dependent Antigens

Cited by 8 publications

References 30 publications

Cbx3/HP1γ deficiency confers enhanced tumor-killing capacity on CD8+ T cells

Cbx3/HP1γ deficiency confers enhanced tumor-killing capacity on CD8+ T cells

The State of Cellular Adoptive Immunotherapy for Neuroblastoma and Other Pediatric Solid Tumors

Heterochromatin protein 1γ deficiency decreases histone H3K27 methylation in mouse neurosphere neuronal genes

Contact Info

Product

Resources

About