Keratinocytes Present Staphylococcus aureus Enterotoxins and Promote Malignant and Nonmalignant T Cell Proliferation in Cutaneous T-Cell Lymphoma.

Publisher: Elsevier Country of Publication: United States NLM ID: 0426720 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-1747 (Electronic) Linking ISSN: 0022202X NLM ISO Abbreviation: J Invest Dermatol Subsets: MEDLINE

Publication: 2016- : New York : Elsevier
Original Publication: Baltimore, Williams & Wilkins.

Enterotoxins*/immunology ; Enterotoxins*/metabolism ; Staphylococcus aureus*/immunology ; Cell Proliferation* ; Skin Neoplasms*/pathology ; Skin Neoplasms*/microbiology ; Skin Neoplasms*/immunology ; Skin Neoplasms*/metabolism ; Lymphoma, T-Cell, Cutaneous*/pathology ; Lymphoma, T-Cell, Cutaneous*/microbiology ; Lymphoma, T-Cell, Cutaneous*/metabolism ; Lymphoma, T-Cell, Cutaneous*/immunology ; Keratinocytes*/metabolism ; Keratinocytes*/immunology ; Keratinocytes*/microbiology ; Tumor Microenvironment*/immunology; Humans ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Sezary Syndrome/pathology ; Sezary Syndrome/immunology ; Sezary Syndrome/metabolism ; Interferon-gamma/metabolism ; Cell Line, Tumor

Cutaneous T-cell lymphoma is characterized by malignant T cells proliferating in a unique tumor microenvironment dominated by keratinocytes (KCs). Skin colonization and infection by Staphylococcus aureus are a common cause of morbidity and are suspected of fueling disease activity. In this study, we show that expression of HLA-DRs, high-affinity receptors for staphylococcal enterotoxins (SEs), by KCs correlates with IFN-γ expression in the tumor microenvironment. Importantly, IFN-γ induces HLA-DR, SE binding, and SE presentation by KCs to malignant T cells from patients with Sézary syndrome and malignant and nonmalignant T-cell lines derived from patients with Sézary syndrome and mycosis fungoides. Likewise, preincubation of KCs with supernatant from patient-derived SE-producing S aureus triggers proliferation in malignant T cells and cytokine release (including IL-2), when cultured with nonmalignant T cells. This is inhibited by pretreatment with engineered bacteriophage S aureus-specific endolysins. Furthermore, alteration in the HLA-DR-binding sites of SE type A and small interfering RNA-mediated knockdown of Jak3 and IL-2Rγ block induction of malignant T-cell proliferation. In conclusion, we show that upon exposure to patient-derived S aureus and SE, KCs stimulate IL-2Rγ/Jak3-dependent proliferation of malignant and nonmalignant T cells in an environment with nonmalignant T cells. These findings suggest that KCs in the tumor microenvironment play a key role in S aureus-mediated disease activity in cutaneous T-cell lymphoma.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Keywords: Cutaneous T-cell lymphoma; Keratinocyte; Staphylococcus aureus

0 (Enterotoxins)
82115-62-6 (Interferon-gamma)

Date Created: 20240518 Date Completed: 20241121 Latest Revision: 20241121

20250114

10.1016/j.jid.2024.04.018

38762064