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JAK1/2 inhibition impairs T cell function in vitro and in patients with myeloproliferative neoplasms

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JAK1/2 inhibition impairs T cell function in vitro and in patients with myeloproliferative neoplasms. / Parampalli Yajnanarayana, Sowmya; Stübig, Thomas; Cornez, Isabelle; Alchalby, Haefaa; Schönberg, Kathrin; Rudolph, Janna; Triviai, Ioanna; Wolschke, Christine; Heine, Annkristin; Brossart, Peter; Kröger, Nicolaus; Wolf, Dominik.

In: BRIT J HAEMATOL, Vol. 169, No. 6, 30.03.2015, p. 824-33.

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

Harvard

Parampalli Yajnanarayana, S, Stübig, T, Cornez, I, Alchalby, H, Schönberg, K, Rudolph, J, Triviai, I, Wolschke, C, Heine, A, Brossart, P, Kröger, N & Wolf, D 2015, 'JAK1/2 inhibition impairs T cell function in vitro and in patients with myeloproliferative neoplasms', BRIT J HAEMATOL, vol. 169, no. 6, pp. 824-33. https://doi.org/10.1111/bjh.13373

APA

Parampalli Yajnanarayana, S., Stübig, T., Cornez, I., Alchalby, H., Schönberg, K., Rudolph, J., Triviai, I., Wolschke, C., Heine, A., Brossart, P., Kröger, N., & Wolf, D. (2015). JAK1/2 inhibition impairs T cell function in vitro and in patients with myeloproliferative neoplasms. BRIT J HAEMATOL, 169(6), 824-33. https://doi.org/10.1111/bjh.13373

Vancouver

Parampalli Yajnanarayana S, Stübig T, Cornez I, Alchalby H, Schönberg K, Rudolph J et al. JAK1/2 inhibition impairs T cell function in vitro and in patients with myeloproliferative neoplasms. BRIT J HAEMATOL. 2015 Mar 30;169(6):824-33. https://doi.org/10.1111/bjh.13373

Bibtex

@article{7ffb8fa8636841c396377b01aa4f9e09,
title = "JAK1/2 inhibition impairs T cell function in vitro and in patients with myeloproliferative neoplasms",
abstract = "Ruxolitinib (INCB018424) is the first JAK1/JAK2 inhibitor approved for treatment of myelofibrosis. JAK/STAT-signalling is known to be involved in the regulation of CD4(+) T cells, which critically orchestrate inflammatory responses. To better understand how ruxolitinib modulates CD4(+) T cell responses, we undertook an in-depth analysis of CD4(+) T cell function upon ruxolitinib exposure. We observed a decrease in total CD3(+) cells after 3 weeks of ruxolitinib treatment in patients with myeloproliferative neoplasms. Moreover, we found that the number of regulatory T cells (Tregs), pro-inflammatory T-helper cell types 1 (Th1) and Th17 were reduced, which were validated by in vitro studies. In line with our in vitro data, we found that inflammatory cytokines [tumour necrosis factor-α (TNF), interleukin (IL)5, IL6, IL1B] were also downregulated in T cells from patients (all P < 0·05). Finally, we showed that ruxolitinib does not interfere with the T cell receptor signalling pathway, but impacts IL2-dependent STAT5 activation. These data provide a rationale for testing JAK inhibitors in diseases triggered by hyperactive CD4(+) T cells, such as autoimmune diseases. In addition, they also provide a potential explanation for the increased infection rates (i.e. viral reactivation and urinary tract infection) seen in ruxolitinib-treated patients.",
author = "{Parampalli Yajnanarayana}, Sowmya and Thomas St{\"u}big and Isabelle Cornez and Haefaa Alchalby and Kathrin Sch{\"o}nberg and Janna Rudolph and Ioanna Triviai and Christine Wolschke and Annkristin Heine and Peter Brossart and Nicolaus Kr{\"o}ger and Dominik Wolf",
note = "{\textcopyright} 2015 John Wiley & Sons Ltd.",
year = "2015",
month = mar,
day = "30",
doi = "10.1111/bjh.13373",
language = "English",
volume = "169",
pages = "824--33",
journal = "BRIT J HAEMATOL",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "6",

}

RIS

TY - JOUR

T1 - JAK1/2 inhibition impairs T cell function in vitro and in patients with myeloproliferative neoplasms

AU - Parampalli Yajnanarayana, Sowmya

AU - Stübig, Thomas

AU - Cornez, Isabelle

AU - Alchalby, Haefaa

AU - Schönberg, Kathrin

AU - Rudolph, Janna

AU - Triviai, Ioanna

AU - Wolschke, Christine

AU - Heine, Annkristin

AU - Brossart, Peter

AU - Kröger, Nicolaus

AU - Wolf, Dominik

N1 - © 2015 John Wiley & Sons Ltd.

PY - 2015/3/30

Y1 - 2015/3/30

N2 - Ruxolitinib (INCB018424) is the first JAK1/JAK2 inhibitor approved for treatment of myelofibrosis. JAK/STAT-signalling is known to be involved in the regulation of CD4(+) T cells, which critically orchestrate inflammatory responses. To better understand how ruxolitinib modulates CD4(+) T cell responses, we undertook an in-depth analysis of CD4(+) T cell function upon ruxolitinib exposure. We observed a decrease in total CD3(+) cells after 3 weeks of ruxolitinib treatment in patients with myeloproliferative neoplasms. Moreover, we found that the number of regulatory T cells (Tregs), pro-inflammatory T-helper cell types 1 (Th1) and Th17 were reduced, which were validated by in vitro studies. In line with our in vitro data, we found that inflammatory cytokines [tumour necrosis factor-α (TNF), interleukin (IL)5, IL6, IL1B] were also downregulated in T cells from patients (all P < 0·05). Finally, we showed that ruxolitinib does not interfere with the T cell receptor signalling pathway, but impacts IL2-dependent STAT5 activation. These data provide a rationale for testing JAK inhibitors in diseases triggered by hyperactive CD4(+) T cells, such as autoimmune diseases. In addition, they also provide a potential explanation for the increased infection rates (i.e. viral reactivation and urinary tract infection) seen in ruxolitinib-treated patients.

AB - Ruxolitinib (INCB018424) is the first JAK1/JAK2 inhibitor approved for treatment of myelofibrosis. JAK/STAT-signalling is known to be involved in the regulation of CD4(+) T cells, which critically orchestrate inflammatory responses. To better understand how ruxolitinib modulates CD4(+) T cell responses, we undertook an in-depth analysis of CD4(+) T cell function upon ruxolitinib exposure. We observed a decrease in total CD3(+) cells after 3 weeks of ruxolitinib treatment in patients with myeloproliferative neoplasms. Moreover, we found that the number of regulatory T cells (Tregs), pro-inflammatory T-helper cell types 1 (Th1) and Th17 were reduced, which were validated by in vitro studies. In line with our in vitro data, we found that inflammatory cytokines [tumour necrosis factor-α (TNF), interleukin (IL)5, IL6, IL1B] were also downregulated in T cells from patients (all P < 0·05). Finally, we showed that ruxolitinib does not interfere with the T cell receptor signalling pathway, but impacts IL2-dependent STAT5 activation. These data provide a rationale for testing JAK inhibitors in diseases triggered by hyperactive CD4(+) T cells, such as autoimmune diseases. In addition, they also provide a potential explanation for the increased infection rates (i.e. viral reactivation and urinary tract infection) seen in ruxolitinib-treated patients.

U2 - 10.1111/bjh.13373

DO - 10.1111/bjh.13373

M3 - SCORING: Journal article

C2 - 25824483

VL - 169

SP - 824

EP - 833

JO - BRIT J HAEMATOL

JF - BRIT J HAEMATOL

SN - 0007-1048

IS - 6

ER -