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Staphylococcus aureus enterotoxins induce FOXP3 in neoplastic T cells in Sézary syndrome.
- Source :
-
Blood cancer journal [Blood Cancer J] 2020 May 14; Vol. 10 (5), pp. 57. Date of Electronic Publication: 2020 May 14. - Publication Year :
- 2020
-
Abstract
- Sézary syndrome (SS) is a heterogeneous leukemic subtype of cutaneous T-cell lymphoma (CTCL) with generalized erythroderma, lymphadenopathy, and a poor prognosis. Advanced disease is invariably associated with severe immune dysregulation and the majority of patients die from infectious complications caused by microorganisms such as, Staphylococcus aureus, rather than from the lymphoma per se. Here, we examined if staphylococcal enterotoxins (SE) may shape the phenotype of malignant SS cells, including expression of the regulatory T-cell-associated marker FOXP3. Our studies with primary and cultured malignant cells show that SE induce expression of FOXP3 in malignant cells when exposed to nonmalignant cells. Mutations in the MHC class II binding domain of SE-A (SEA) largely block the effect indicating that the response relies at least in part on the MHC class II-mediated antigen presentation. Transwell experiments show that the effect is induced by soluble factors, partly blocked by anti-IL-2 antibody, and depends on STAT5 activation in malignant cells. Collectively, these findings show that SE stimulate nonmalignant cells to induce FOXP3 expression in malignant cells. Thus, differences in exposure to environmental factors, such as bacterial toxins may explain the heterogeneous FOXP3 expression in malignant cells in SS.
- Subjects :
- Cell Line, Tumor
Forkhead Transcription Factors immunology
Humans
Sezary Syndrome complications
Sezary Syndrome genetics
Skin Neoplasms complications
Skin Neoplasms genetics
Staphylococcal Infections complications
Staphylococcal Infections genetics
T-Lymphocytes immunology
T-Lymphocytes metabolism
Tumor Cells, Cultured
Up-Regulation
Enterotoxins immunology
Forkhead Transcription Factors genetics
Sezary Syndrome immunology
Skin Neoplasms immunology
Staphylococcal Infections immunology
Staphylococcus aureus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2044-5385
- Volume :
- 10
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Blood cancer journal
- Publication Type :
- Academic Journal
- Accession number :
- 32409671
- Full Text :
- https://doi.org/10.1038/s41408-020-0324-3