Enhanced proliferation and defective activation-induced cell death of CD4+ T cells in childhood asthma

Jiang, Tingwang; Sheng, Jian-hua; Qin, Yimin; Xiong, Huai-min; Gong, Yanping; Tang, Hao; Zhou, Jinbao; Deng, Zhengbo; Zhang, Hongxing; Cui, Yinghong; Qian, Jiang; Shen, Yue; Jin, Yi

doi:10.12932/ap0332.32.1.2014

Cited by 11 publications

(20 citation statements)

References 29 publications

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“…The data show that inhibition of Bcl2L12 restores the apoptotic machinery in AR CD4 + T cells. Previous studies show defects of apoptosis in CD4 + T cells collected from patients with allergic asthma, suggesting that defects of apoptosis may contribute to the pathogenesis of allergic asthma . The present data provide mechanistic evidence to explain that the increase in expression of Bcl2L12 in CD4 + T cells may be the reason or one of the reasons of Th2 polarization in AR patients.…”

Section: Discussionsupporting

confidence: 67%

“…21 gesting that defects of apoptosis may contribute to the pathogenesis of allergic asthma. 11 The present data provide mechanistic evidence to explain that the increase in expression of Bcl2L12 in CD4 + T cells may be the reason or one of the reasons of Th2 polarization in AR patients.…”

Section: Discussionmentioning

confidence: 54%

“…10 It was observed that the AICD machinery in CD4 + T cells was impaired in patients with allergic asthma. 11 This may contribute to Th2 polarization. The phenomenon implies the expression and functions of some regulatory factors of apoptosis in CD4 + T cells may be unusually changed.…”

Section: Introductionmentioning

confidence: 99%

“…The activated T cells die from apoptosis . It was observed that the AICD machinery in CD4 + T cells was impaired in patients with allergic asthma . This may contribute to Th2 polarization.…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-5 induces apoptotic defects in CD4+ T cells of patients with allergic rhinitis

Luo

Wang

et al. 2019

Journal of Leukocyte Biology

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T helper (Th)2 polarization plays an important role in the pathogenesis of allergic diseases; the underlying mechanism remains to be further investigated. B cell lymphoma protein‐2 like protein‐12 (Bcl2L12) has the anti‐apoptotic function. This study aims to elucidate the contribution of Bcl2L12 to Th2 polarization in patients with allergic rhinitis (AR). In this study, human CD4+ T cells were isolated from blood samples collected from AR patients and healthy control (HC) subjects. The immune response profiles of CD4+ T cells were analyzed by immunologic approaches. The results showed that AR CD4+ T cells (CD4+ T cells collected from AR patients) showed defects of apoptosis. The expression of FasL in AR CD4+ T cells was lower than that of HC CD4+ T cells. Serum IL‐5 levels were negatively correlated with the expression of FasL in AR CD4+ T cells. Exposure of CD4+ T cells to IL‐5 in the culture suppressed the expression of FasL and increased the expression of Bcl2L12. IL‐5 increased the levels of Bcl2L12 in CD4+ T cells, the latter bound to the FasL promoter to prevent FasL gene transcription. Inhibition of Bcl2L12 restored the apoptosis machinery in AR CD4+ T cells. In conclusion, overexpression of Bcl2L12 in CD4+ T cells compromises the apoptosis machinery; the latter can be restored by inhibition of Bcl2L12. BcL2L12 in CD4+ T cells may be a novel target for the treatment of AR and other allergic disorders.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Interleukin-5 induces apoptotic defects in CD4+ T cells of patients with allergic rhinitis

Luo

Wang

et al. 2019

Journal of Leukocyte Biology

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“…Cell proliferation was assessed with a cell-counting kit (CCK)-8 assay (Signalway Antibody Co., Maryland, TX, USA) as previously described [23]. Before the assay, spleen lymphocytes from each experimental group were freshly isolated and seeded in 96-well plates at a density of 3 × 10 4 cells/100 μL, and then cultured for 24, 48, and 72 h. CCK-8 solution (10 μL) was added to each well of the plate.…”

Section: Cell-counting Kit-8 Assay For Proliferation Of Lymphocytesmentioning

confidence: 99%

Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model

Huang²,

Zhu

et al. 2018

Int Arch Allergy Immunol

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Background: Specific immunotherapy, including agonists for Toll-like receptor 2 (TLR2), have been shown to protect from allergies and to have a high immunomodulatory capacity. Methods: A new antibody, TSP-2, reactive against an epitope of the extracellular domain of TLR2, was identified. The effect of the antibody on dendritic cells was assessed by immunohistochemistry, Western blot, and flow cytometric analysis. The effect of TSP-2 in a murine asthma model induced with ovalbumin (OVA) was assessed. The model is a form of airway hyperresponsiveness (AHR) and was analyzed by whole-body plethysmography, the measurement of Th1/Th2 cytokines in bronchial alveolar lavage fluid (BALF) and serum by ELISA, and the CCK-8 assay for lymphocyte proliferation. The effect of TSP-2 on the maturation of bone marrow-derived dendritic cells (BMDCs) was assessed by flow cytometric analysis. Results: TSP-2 promoted the maturation of dendritic cells and the proliferation of lymphocyte in vitro and in vivo. The effect of TSP-2 on T helper 1 (Th1)/Th2 cytokine secretion was slightly more powerful than that of Pam₃CSK₄. TSP-2 antibody reduced AHR and OVA-specific IgE levels in allergic asthma. TSP-2 antibody also reduced lung inflammation and decreased leukocyte numbers in an OVA-sensitized and challenged asthma model. TSP-2 antibody increased OVA-stimulated I-A, CD80, CD86, and MHC-II levels on BMDCs. Conclusions: This study identifies a novel therapeutic strategy for AHR, which uses antibodies reactive against TLR2. It also provides theoretical evidence for the control of allergic asthma by targeting TLR2.

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Bcl2L12 plays a critical role in the development of intestinal allergy

Feng

Hong

et al. 2018

Immunology Letters

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Enhanced proliferation and defective activation-induced cell death of CD4+ T cells in childhood asthma

Cited by 11 publications

References 29 publications

Interleukin-5 induces apoptotic defects in CD4+ T cells of patients with allergic rhinitis

Interleukin-5 induces apoptotic defects in CD4+ T cells of patients with allergic rhinitis

Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model

Bcl2L12 plays a critical role in the development of intestinal allergy

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