Role of Fas–Fas Ligand Interactions in 2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD)-Induced Immunotoxicity: Increased Resistance of Thymocytes from Fas-Deficient (lpr) and Fas Ligand-Defective (gld) Mice to TCDD-Induced Toxicity

Abstract HLA class II molecules, expressed on the surface of antigen-presenting cells, are responsible for the presentation of antigen-derived peptides to CD4+ helper T lymphocytes. Signaling via these molecules initiates the generation of second messengers leading to programed cell death (PCD) of activated B lymphocytes. The present study examined the mechanism of HLA class II–mediated apoptosis and describes the essential role of the molecule Fas and its ligand (FasL). FasL was expressed in B lymphocytes after stimulation via HLA class II or with phorbol esters. Expression of FasL protein was significantly increased in 50% of B lymphocytes after stimulation via HLA class II, and the level of FasL mRNA was also increased either by activation with phorbol esters and ionomycin or by signaling via HLA class II. Although HLA class II signaling did not change the expression of the Fas molecule, it did lead to increased sensitivity to Fas-mediated apoptosis. The crucial role of Fas/FasL interactions was confirmed by the absence of cell death via HLA class II in B cells lacking Fas expression, and by the significant inhibition of HLA class II–mediated apoptosis in the presence of either an antagonistic anti-Fas or anti-FasL antibody. These data demonstrate FasL expression on activated human B lymphocytes and support the idea that antigen presentation could contribute to the regulation of lymphocyte populations via Fas and FasL interactions.

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Differential Role of Fas/Fas Ligand Interactions in Cytolysis of Primary and Metastatic Colon Carcinoma Cell Lines by Human Antigen-Specific CD8+CTL

The Journal of Immunology ◽

10.4049/jimmunol.164.9.4941 ◽

2000 ◽

Vol 164 (9) ◽

pp. 4941-4954 ◽

Cited By ~ 30

Author(s):

Elke S. Bergmann-Leitner ◽

Scott I. Abrams

Keyword(s):

Colon Carcinoma ◽

Cell Lines ◽

Fas Ligand ◽

Carcinoma Cell ◽

Carcinoma Cell Lines ◽

Ligand Interactions ◽

Metastatic Colon Carcinoma

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Activated CD4+ T cells enriched from spleen or colon induce apoptosis in intestinal epithellal cells via fas/fas ligand interactions

Gastroenterology ◽

10.1016/s0016-5085(01)80949-5 ◽

2001 ◽

Vol 120 (5) ◽

pp. A192-A192

Author(s):

H TAKAISHI ◽

T DENNING ◽

K ITO ◽

R MIFFLIN ◽

P ERNST

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Fas Ligand ◽

Ligand Interactions

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The Potential Role of DNA Methylation in the Response to 2,3,7,8-Tetrachlorodibenzo-p-dioxin

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)84636-7 ◽

1989 ◽

Vol 264 (30) ◽

pp. 17754-17758 ◽

Cited By ~ 1

Author(s):

E S Shen ◽

J P Whitlock

Keyword(s):

Dna Methylation ◽

Potential Role ◽

Tetrachlorodibenzo P Dioxin

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sFasL—The Key to a Riddle: Immune Responses in Aging Lung and Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22042177 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2177

Author(s):

Shulamit B. Wallach-Dayan ◽

Dmytro Petukhov ◽

Ronit Ahdut-HaCohen ◽

Mark Richter-Dayan ◽

Raphael Breuer

Keyword(s):

Cell Death ◽

Lung Disease ◽

Fas Ligand ◽

Death Receptor ◽

Mesenchymal Cells ◽

Soluble Form ◽

Cell Accumulation ◽

Key Factor ◽

Aged Subjects

By dint of the aging population and further deepened with the Covid-19 pandemic, lung disease has turned out to be a major cause of worldwide morbidity and mortality. The condition is exacerbated when the immune system further attacks the healthy, rather than the diseased, tissue within the lung. Governed by unremittingly proliferating mesenchymal cells and increased collagen deposition, if inflammation persists, as frequently occurs in aging lungs, the tissue develops tumors and/or turns into scars (fibrosis), with limited regenerative capacity and organ failure. Fas ligand (FasL, a ligand of the Fas cell death receptor) is a key factor in the regulation of these processes. FasL is primarily found in two forms: full length (membrane, or mFasL) and cleaved (soluble, or sFasL). We and others found that T-cells expressing the mFasL retain autoimmune surveillance that controls mesenchymal, as well as tumor cell accumulation following an inflammatory response. However, mesenchymal cells from fibrotic lungs, tumor cells, or cells from immune-privileged sites, resist FasL+ T-cell-induced cell death. The mechanisms involved are a counterattack of immune cells by FasL, by releasing a soluble form of FasL that competes with the membrane version, and inhibits their cell death, promoting cell survival. This review focuses on understanding the previously unrecognized role of FasL, and in particular its soluble form, sFasL, in the serum of aged subjects, and its association with the evolution of lung disease, paving the way to new methods of diagnosis and treatment.

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