Epstein–Barr virus-positive pyothorax-associated lymphoma expresses CCL17 and CCL22 chemokines that attract CCR4-expressing regulatory T cells

Higuchi, Tomonori; Matsuo, Keitaro; Hashida, Yumiko; Kitahata, Kosuke; Ujihara, Takako; Taniguchi, Ayuko; Yoshie, Osamu; Nakayama, Takashi; Daibata, Masanori

doi:10.1016/j.canlet.2019.03.053

Cited by 17 publications

(14 citation statements)

References 46 publications

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“…cd4 + cd25 + Foxp3 + Treg cells in patients with solid tumors have been reported to be attracted to and activated by chemokines (19,20,31). Increased infiltration of CD4 + cd25 + Foxp3 + Treg cells was observed in Bc tissues and was associated with high histologic grade, negative estrogen receptor and progesterone receptor status, and human epidermal growth factor receptor type 2 overexpression, as well as decreased overall and progression-free survival (32).…”

Section: Discussionmentioning

confidence: 99%

“…ab171870; abcam) for 48 h at 4˚C. CD4 + T cells were isolated from the PBMcs of healthy individuals and 1x10 5 cd4 + T cells were treated with different concentrations of recombinant human ccl11 protein (5,10,20, 50 and 100 ng/ml; cat. no.…”

Section: Methodsmentioning

confidence: 99%

“…There is evidence that certain malignant phenotypes of cells release chemokines, including ccl2, ccl5 and ccl22, to attract and activate Treg cells (19,20). ccl11 was reported to limit angiogenesis and cause necrosis in a murine model of osteosarcoma by inducing and attracting eosinophils and reducing the tumor formation ability (21).…”

Section: Introductionmentioning

confidence: 99%

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CCL11 increases the proportion of CD4+CD25+Foxp3+ Treg cells and the production of IL‑2 and TGF‑β by CD4+ T�cells via the STAT5 signaling pathway

Wang

Huang

2020

Mol Med Report

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cd4 + regulatory T (Treg) cells are associated with immune tolerance and antitumor immunosuppression. The aim of the present study was to investigate the role and molecular mechanism of c-c motif chemokine ligand 11 (ccl11) in the regulation of Treg cells from patients with breast cancer (Bc) and healthy individuals in vitro, and from tumor-bearing mice in vivo. cd4 + T cells isolated from patients with Bc or healthy individuals were incubated with anti-ccl11 neutralizing antibodies or recombinant human ccl11 protein, in the presence or absence of a STaT5 inhibitor. The serum ccl11 level and proportion of Treg cells characterized as cd4 + cd25 + forkhead box P3 + (Foxp3) among the cd4 + T cells in patients with Bc and healthy individuals were analyzed by eliSa and flow cytometry, respectively. CCL11, C-C motif chemokine receptor 3 (ccr3), Foxp3, phosphorylated-STaT5 and STaT5 expression levels were determined by western blotting. The serum ccl11 level and the proportion of cd4 + cd25 + Foxp3 + Treg cells were significantly increased in patients with BC compared with healthy individuals. ccl11 blockade reduced the proportion of cd4 + cd25 + Foxp3 + Treg cells, the expression of ccr3 and Foxp3, and the level of STaT5 activation in tumor-associated cd4 + T cells, in a dose-dependent manner. ccl11 blockade also reduced the proportion of cd4 + cd25 + Foxp3 + Treg cells and the serum levels of interleukin (il)-2 and transforming growth factor (TGF)-β1 in tumor-bearing mice. The recombinant human ccl11 protein increased the proportion of cd4 + cd25 + Foxp3 + Treg cells, the expression of ccr3 and Foxp3, and the release of il-2 and TGF-β1 in non-tumor-associated cd4 + T cells via the STaT5 signaling pathway. The results of the present study may aid in identifying therapeutics that could further modulate the immune system during Bc.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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CCL11 increases the proportion of CD4+CD25+Foxp3+ Treg cells and the production of IL‑2 and TGF‑β by CD4+ T�cells via the STAT5 signaling pathway

Wang

Huang

2020

Mol Med Report

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“…Chronic inflammation at the local site perhaps plays a role in the proliferation of EBV-transformed B cells, since it allows them to escape from the host immune surveillance, as a result of the production of immunosuppressive IL10 cytokine, and the autocrine to paracrine growth via IL6 and IL6R [ 2 ]. Furthermore, EBV + DLBCL associated with chronic inflammation expresses CCL17 and CCL22 chemokines that are involved in the recruitment of CCR4-expressing regulatory T cells at the microenvironment [ 113 ]. In addition, downregulation of HLA class I expression, and mutations of cytotoxic T-lymphocyte epitopes in EBNA3B, an immunodominant antigen for cytotoxic T-lymphocyte responses, could also contribute to escape of neoplastic cells from host cytotoxic T lymphocytes [ 2 ].…”

Section: Dlbcl Associated With Chronic Inflammationmentioning

confidence: 99%

Advances in the Pathogenesis of EBV-Associated Diffuse Large B Cell Lymphoma

Chabay

2021

Cancers

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Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin’s lymphoma (NHL) in adults. Epstein–Barr virus (EBV) positive DLBCL of the elderly was defined by the World Health Organization (WHO) in 2008, it was restricted only to patients older than 50 years old, and it was attributed to immunesenescence associated with physiological aging. After the description of EBV-associated DLBCL in children and young adults, the WHO redefined the definition, leading to the substitution of the modifier “elderly” with “not otherwise specified” (EBV + DLBCL, NOS) in the updated classification, and it is no more considered provisional. The incidence of EBV + DLBCL, NOS varies around the world, in particular influenced by the percentage of EBV+ cells used as cut-off to define a case as EBV-associated. EBV has effect on the genetic composition of tumor cells, on survival, and at the recruitment of immune cells at the microenvironment. In this review, the role of EBV in the pathogenesis of DLBCL is discussed.

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“…The mechanism of Treg recruitment in PE has not been fully elucidated. However, in other diseases, such as carcinoma [37,38], auto immune diseases [39], infections [40,41], or implantation [42,43], CCL22, the macrophage derived chemokine, and its receptor, CCR4, are well known for their role in the migration of Tregs [44]. CCL22 is produced by certain types of immune cells, such as macrophages, monocyte-derived dendritic cells [45,46], NK cells, and activated T cells [47].…”

Section: Introductionmentioning

confidence: 99%

Regulatory T Cell Apoptosis during Preeclampsia May Be Prevented by Gal-2

Meister

Hahn

Beyer

et al. 2022

IJMS

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There are several open questions to be answered regarding the pathophysiology of the development of preeclampsia (PE). Numerous factors are involved in its genesis, such as defective placentation, vascular impairment, and an altered immune response. The activation of the adaptive and innate immune system represents an immunologic, particularity during PE. Proinflammatory cytokines are predominantly produced, whereas immune regulatory and immune suppressive factors are diminished in PE. In the present study, we focused on the recruitment of regulatory T cells (Tregs) which are key players in processes mediating immune tolerance. To identify Tregs in the decidua, an immunohistochemical staining of FoxP3 of 32 PE and 34 control placentas was performed. A clearly reduced number of FoxP3-positive cells in the decidua of preeclamptic women could be shown in our analysis (p = 0.036). Furthermore, CCL22, a well-known Treg chemoattractant, was immunohistochemically evaluated. Interestingly, CCL22 expression was increased at the maternal-fetal interface in PE-affected pregnancies (psyncytiotrophoblast = 0.035, pdecidua = 0.004). Therefore, the hypothesis that Tregs undergo apoptosis at the materno-fetal interface during PE was generated, and verified by FoxP3/TUNEL (TdT-mediated dUTP-biotin nick end labeling) staining. Galectin-2 (Gal-2), a member of the family of carbohydrate-binding proteins, which is known to be downregulated during PE, seems to play a pivotal role in T cell apoptosis. By performing a cell culture experiment with isolated Tregs, we could identify Gal-2 as a factor that seems to prevent the apoptosis of Tregs. Our findings point to a cascade of apoptosis of Tregs at the materno-fetal interface during PE. Gal-2 might be a potential therapeutic target in PE to regulate immune tolerance.

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Epstein–Barr virus-positive pyothorax-associated lymphoma expresses CCL17 and CCL22 chemokines that attract CCR4-expressing regulatory T cells

Cited by 17 publications

References 46 publications

CCL11 increases the proportion of CD4+CD25+Foxp3+ Treg cells and the production of IL‑2 and TGF‑β by CD4+ T�cells via the STAT5 signaling pathway

CCL11 increases the proportion of CD4+CD25+Foxp3+ Treg cells and the production of IL‑2 and TGF‑β by CD4+ T�cells via the STAT5 signaling pathway

Advances in the Pathogenesis of EBV-Associated Diffuse Large B Cell Lymphoma

Regulatory T Cell Apoptosis during Preeclampsia May Be Prevented by Gal-2

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