Malignant Tregs express low molecular splice forms of FOXP3 in Sézary syndrome

T Krejsgaard; L M Gjerdrum; E Ralfkiaer; B Lauenborg; K W Eriksen; A-M Mathiesen; L F Bovin; R Gniadecki; C Geisler; L P Ryder; Q Zhang; M A Wasik; Niels Odum; A Woetmann

doi:10.1038/leu.2008.224

Malignant Tregs express low molecular splice forms of FOXP3 in Sézary syndrome

T Krejsgaard, L M Gjerdrum, E Ralfkiaer, B Lauenborg, K W Eriksen, A-M Mathiesen, L F Bovin, R Gniadecki, C Geisler, L P Ryder, Q Zhang, M A Wasik, Niels Odum, A Woetmann

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

80 Citationer (Scopus)

Abstract

Udgivelsesdato: 2008-Sep-4

Originalsprog	Engelsk
Tidsskrift	Leukemia
Sider (fra-til)	2230-2239
Antal sider	9
ISSN	0887-6924
DOI	https://doi.org/10.1038/leu.2008.224
Status	Udgivet - 2008

Adgang til dokumentet

10.1038/leu.2008.224

Citationsformater

Malignant Tregs express low molecular splice forms of FOXP3 in Sézary syndrome. / Krejsgaard, T; Gjerdrum, L M; Ralfkiaer, E; Lauenborg, B; Eriksen, K W; Mathiesen, A-M; Bovin, L F; Gniadecki, R; Geisler, C; Ryder, L P; Zhang, Q; Wasik, M A; Odum, Niels ; Woetmann, A.

I: Leukemia, 2008, s. 2230-2239.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

@article{5530d2c0b09d11ddb538000ea68e967b,

title = "Malignant Tregs express low molecular splice forms of FOXP3 in S{\'e}zary syndrome",

abstract = "S{\'e}zary syndrome (SS) is an aggressive variant of cutaneous T-cell lymphoma. During disease progression, immunodeficiency develops; however, the underlying molecular and cellular mechanisms are not fully understood. Here, we study the regulatory T cell (Treg) function and the expression of FOXP3 in SS. We demonstrate that malignant T cells in 8 of 15 patients stain positive with an anti-FOXP3 antibody. Western blotting analysis shows expression of two low molecular splice forms of FOXP3, but not of wild-type (wt) FOXP3. The malignant T cells produce interleukin-10 and TGF-beta and suppress the growth of non-malignant T cells. The Treg phenotype and the production of suppressive cytokines are driven by aberrant activation of Jak3 independent of the FOXP3 splice forms. In contrast to wt FOXP3, the low molecular splice forms of FOXP3 have no inhibitory effect on nuclear factor-kappaB (NF-kappaB) activity in reporter assays which is in keeping with a constitutive NF-kappaB activity in the malignant T cells. In conclusion, we show that the malignant T cells express low molecular splice forms of FOXP3 and function as Tregs. Furthermore, we provide evidence that FOXP3 splice forms are functionally different from wt FOXP3 and not involved in the execution of the suppressive function. Thus, this is the first description of FOXP3 splice forms in human disease.Leukemia advance online publication, 4 September 2008; doi:10.1038/leu.2008.224.",

author = "T Krejsgaard and Gjerdrum, {L M} and E Ralfkiaer and B Lauenborg and Eriksen, {K W} and A-M Mathiesen and Bovin, {L F} and R Gniadecki and C Geisler and Ryder, {L P} and Q Zhang and Wasik, {M A} and Niels Odum and A Woetmann",

year = "2008",

doi = "10.1038/leu.2008.224",

language = "English",

pages = "2230--2239",

journal = "Leukemia",

issn = "0887-6924",

publisher = "nature publishing group",

}

TY - JOUR

T1 - Malignant Tregs express low molecular splice forms of FOXP3 in Sézary syndrome

AU - Krejsgaard, T

AU - Gjerdrum, L M

AU - Ralfkiaer, E

AU - Lauenborg, B

AU - Eriksen, K W

AU - Mathiesen, A-M

AU - Bovin, L F

AU - Gniadecki, R

AU - Geisler, C

AU - Ryder, L P

AU - Zhang, Q

AU - Wasik, M A

AU - Odum, Niels

AU - Woetmann, A

PY - 2008

Y1 - 2008

N2 - Sézary syndrome (SS) is an aggressive variant of cutaneous T-cell lymphoma. During disease progression, immunodeficiency develops; however, the underlying molecular and cellular mechanisms are not fully understood. Here, we study the regulatory T cell (Treg) function and the expression of FOXP3 in SS. We demonstrate that malignant T cells in 8 of 15 patients stain positive with an anti-FOXP3 antibody. Western blotting analysis shows expression of two low molecular splice forms of FOXP3, but not of wild-type (wt) FOXP3. The malignant T cells produce interleukin-10 and TGF-beta and suppress the growth of non-malignant T cells. The Treg phenotype and the production of suppressive cytokines are driven by aberrant activation of Jak3 independent of the FOXP3 splice forms. In contrast to wt FOXP3, the low molecular splice forms of FOXP3 have no inhibitory effect on nuclear factor-kappaB (NF-kappaB) activity in reporter assays which is in keeping with a constitutive NF-kappaB activity in the malignant T cells. In conclusion, we show that the malignant T cells express low molecular splice forms of FOXP3 and function as Tregs. Furthermore, we provide evidence that FOXP3 splice forms are functionally different from wt FOXP3 and not involved in the execution of the suppressive function. Thus, this is the first description of FOXP3 splice forms in human disease.Leukemia advance online publication, 4 September 2008; doi:10.1038/leu.2008.224.

AB - Sézary syndrome (SS) is an aggressive variant of cutaneous T-cell lymphoma. During disease progression, immunodeficiency develops; however, the underlying molecular and cellular mechanisms are not fully understood. Here, we study the regulatory T cell (Treg) function and the expression of FOXP3 in SS. We demonstrate that malignant T cells in 8 of 15 patients stain positive with an anti-FOXP3 antibody. Western blotting analysis shows expression of two low molecular splice forms of FOXP3, but not of wild-type (wt) FOXP3. The malignant T cells produce interleukin-10 and TGF-beta and suppress the growth of non-malignant T cells. The Treg phenotype and the production of suppressive cytokines are driven by aberrant activation of Jak3 independent of the FOXP3 splice forms. In contrast to wt FOXP3, the low molecular splice forms of FOXP3 have no inhibitory effect on nuclear factor-kappaB (NF-kappaB) activity in reporter assays which is in keeping with a constitutive NF-kappaB activity in the malignant T cells. In conclusion, we show that the malignant T cells express low molecular splice forms of FOXP3 and function as Tregs. Furthermore, we provide evidence that FOXP3 splice forms are functionally different from wt FOXP3 and not involved in the execution of the suppressive function. Thus, this is the first description of FOXP3 splice forms in human disease.Leukemia advance online publication, 4 September 2008; doi:10.1038/leu.2008.224.

U2 - 10.1038/leu.2008.224

DO - 10.1038/leu.2008.224

M3 - Journal article

C2 - 18769452

SP - 2230

EP - 2239

JO - Leukemia

JF - Leukemia

SN - 0887-6924

ER -