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

Research output: Contribution to journal › Journal article › Research › peer-review

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Keratinocytes Present Staphylococcus aureus Enterotoxins and Promote Malignant and Nonmalignant T Cell Proliferation in Cutaneous T-Cell Lymphoma. / Zeng, Ziao; Vadivel, Chella Krishna; Gluud, Maria; Namini, Martin R.J.; Yan, Lang; Ahmad, Sana; Hansen, Morten Bagge; Coquet, Jonathan; Mustelin, Tomas; Koralov, Sergei B.; Bonefeld, Charlotte Menne; Woetmann, Anders; Geisler, Carsten; Guenova, Emmanuella; Kamstrup, Maria R.; Litman, Thomas; Gjerdrum, Lise Mette R.; Buus, Terkild B.; Ødum, Niels.

In: Journal of Investigative Dermatology, 2024.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Zeng, Z, Vadivel, CK, Gluud, M, Namini, MRJ, Yan, L, Ahmad, S, Hansen, MB, Coquet, J, Mustelin, T, Koralov, SB, Bonefeld, CM, Woetmann, A, Geisler, C, Guenova, E, Kamstrup, MR, Litman, T, Gjerdrum, LMR, Buus, TB & Ødum, N 2024, 'Keratinocytes Present Staphylococcus aureus Enterotoxins and Promote Malignant and Nonmalignant T Cell Proliferation in Cutaneous T-Cell Lymphoma', Journal of Investigative Dermatology. https://doi.org/10.1016/j.jid.2024.04.018

APA

Zeng, Z., Vadivel, C. K., Gluud, M., Namini, M. R. J., Yan, L., Ahmad, S., Hansen, M. B., Coquet, J., Mustelin, T., Koralov, S. B., Bonefeld, C. M., Woetmann, A., Geisler, C., Guenova, E., Kamstrup, M. R., Litman, T., Gjerdrum, L. M. R., Buus, T. B., & Ødum, N. (Accepted/In press). Keratinocytes Present Staphylococcus aureus Enterotoxins and Promote Malignant and Nonmalignant T Cell Proliferation in Cutaneous T-Cell Lymphoma. Journal of Investigative Dermatology. https://doi.org/10.1016/j.jid.2024.04.018

Vancouver

Zeng Z, Vadivel CK, Gluud M, Namini MRJ, Yan L, Ahmad S et al. Keratinocytes Present Staphylococcus aureus Enterotoxins and Promote Malignant and Nonmalignant T Cell Proliferation in Cutaneous T-Cell Lymphoma. Journal of Investigative Dermatology. 2024. https://doi.org/10.1016/j.jid.2024.04.018

Author

Zeng, Ziao ; Vadivel, Chella Krishna ; Gluud, Maria ; Namini, Martin R.J. ; Yan, Lang ; Ahmad, Sana ; Hansen, Morten Bagge ; Coquet, Jonathan ; Mustelin, Tomas ; Koralov, Sergei B. ; Bonefeld, Charlotte Menne ; Woetmann, Anders ; Geisler, Carsten ; Guenova, Emmanuella ; Kamstrup, Maria R. ; Litman, Thomas ; Gjerdrum, Lise Mette R. ; Buus, Terkild B. ; Ødum, Niels. / Keratinocytes Present Staphylococcus aureus Enterotoxins and Promote Malignant and Nonmalignant T Cell Proliferation in Cutaneous T-Cell Lymphoma. In: Journal of Investigative Dermatology. 2024.

Bibtex

@article{3e3674b398164ab69ff489c82ad5409c,

title = "Keratinocytes Present Staphylococcus aureus Enterotoxins and Promote Malignant and Nonmalignant T Cell Proliferation in Cutaneous T-Cell Lymphoma",

abstract = "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 S{\'e}zary syndrome and malignant and nonmalignant T-cell lines derived from patients with S{\'e}zary 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.",

keywords = "Cutaneous T-cell lymphoma, Keratinocyte, Staphylococcus aureus",

author = "Ziao Zeng and Vadivel, {Chella Krishna} and Maria Gluud and Namini, {Martin R.J.} and Lang Yan and Sana Ahmad and Hansen, {Morten Bagge} and Jonathan Coquet and Tomas Mustelin and Koralov, {Sergei B.} and Bonefeld, {Charlotte Menne} and Anders Woetmann and Carsten Geisler and Emmanuella Guenova and Kamstrup, {Maria R.} and Thomas Litman and Gjerdrum, {Lise Mette R.} and Buus, {Terkild B.} and Niels {\O}dum",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

doi = "10.1016/j.jid.2024.04.018",

language = "English",

journal = "Journal of Investigative Dermatology",

issn = "0022-202X",

publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Keratinocytes Present Staphylococcus aureus Enterotoxins and Promote Malignant and Nonmalignant T Cell Proliferation in Cutaneous T-Cell Lymphoma

AU - Zeng, Ziao

AU - Vadivel, Chella Krishna

AU - Gluud, Maria

AU - Namini, Martin R.J.

AU - Yan, Lang

AU - Ahmad, Sana

AU - Hansen, Morten Bagge

AU - Coquet, Jonathan

AU - Mustelin, Tomas

AU - Koralov, Sergei B.

AU - Bonefeld, Charlotte Menne

AU - Woetmann, Anders

AU - Geisler, Carsten

AU - Guenova, Emmanuella

AU - Kamstrup, Maria R.

AU - Litman, Thomas

AU - Gjerdrum, Lise Mette R.

AU - Buus, Terkild B.

AU - Ødum, Niels

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - Cutaneous T-cell lymphoma

KW - Keratinocyte

KW - Staphylococcus aureus

U2 - 10.1016/j.jid.2024.04.018

DO - 10.1016/j.jid.2024.04.018

M3 - Journal article

C2 - 38762064

AN - SCOPUS:85195287389

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

ER -

ID: 395144186