BTLA Expression in CLL: Epigenetic Regulation and Impact on CLL B Cell Proliferation and Ability to IL-4 Production
In our previous study, while chronic lymphocytic leukemia (CLL) cases showed higher levels of B and T lymphocyte attenuator (BTLA) mRNA compared to controls, lower BTLA protein expression was observed in cases compared to controls. Hence we hypothesize that micro RNA (miR) 155-5p regulates BTLA expr...
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2021
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oai:doaj.org-article:789b06c2e0d04cf591a5c197ecb1eab92021-11-25T17:10:22ZBTLA Expression in CLL: Epigenetic Regulation and Impact on CLL B Cell Proliferation and Ability to IL-4 Production10.3390/cells101130092073-4409https://doaj.org/article/789b06c2e0d04cf591a5c197ecb1eab92021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3009https://doaj.org/toc/2073-4409In our previous study, while chronic lymphocytic leukemia (CLL) cases showed higher levels of B and T lymphocyte attenuator (BTLA) mRNA compared to controls, lower BTLA protein expression was observed in cases compared to controls. Hence we hypothesize that micro RNA (miR) 155-5p regulates BTLA expression in CLL. In line with earlier data, expression of BTLA mRNA and miR-155-5p is elevated in CLL (<i>p</i> = 0.034 and <i>p</i> = 0.0006, respectively) as well as in MEC-1 cell line (<i>p</i> = 0.009 and 0.016, respectively). Inhibition of miR-155-5p partially restored BTLA protein expression in CLL patients (<i>p</i> = 0.01) and in MEC-1 cell lines (<i>p</i> = 0.058). Additionally, we aimed to evaluate the significance of BTLA deficiency in CLL cells on proliferation and IL-4 production of B cells. We found that secretion of IL-4 is not dependent on BTLA expression, since fractions of BTLA positive and BTLA negative B cells expressing intracellular IL-4 were similar in CLL patients and controls. We demonstrated that in controls the fraction of proliferating cells is lower in BTLA positive than in BTLA negative B cells (<i>p</i> = 0.059), which was not observed in CLL. However, the frequency of BTLA positive Ki67+ B cells in CLL was higher compared to corresponding cells from controls (<i>p</i> = 0.055) while there were no differences between the examined groups regarding frequency of BTLA negative Ki67+ B cells. Our studies suggest that miR-155-5p is involved in BTLA deficiency, affecting proliferation of CLL B cells, which may be one of the mechanisms responsible for CLL pathogenesis.Lidia KarabonAnna AndrzejczakLidia CiszakAnna TomkiewiczAleksandra SzteblichAgnieszka Bojarska-JunakJacek RolińskiDariusz WołowiecTomasz WróbelAgata KosmaczewskaMDPI AGarticleCLLBTLAIL-4proliferationepigenetic regulationmiR-155-5pBiology (General)QH301-705.5ENCells, Vol 10, Iss 3009, p 3009 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
CLL BTLA IL-4 proliferation epigenetic regulation miR-155-5p Biology (General) QH301-705.5 |
| spellingShingle |
CLL BTLA IL-4 proliferation epigenetic regulation miR-155-5p Biology (General) QH301-705.5 Lidia Karabon Anna Andrzejczak Lidia Ciszak Anna Tomkiewicz Aleksandra Szteblich Agnieszka Bojarska-Junak Jacek Roliński Dariusz Wołowiec Tomasz Wróbel Agata Kosmaczewska BTLA Expression in CLL: Epigenetic Regulation and Impact on CLL B Cell Proliferation and Ability to IL-4 Production |
| description |
In our previous study, while chronic lymphocytic leukemia (CLL) cases showed higher levels of B and T lymphocyte attenuator (BTLA) mRNA compared to controls, lower BTLA protein expression was observed in cases compared to controls. Hence we hypothesize that micro RNA (miR) 155-5p regulates BTLA expression in CLL. In line with earlier data, expression of BTLA mRNA and miR-155-5p is elevated in CLL (<i>p</i> = 0.034 and <i>p</i> = 0.0006, respectively) as well as in MEC-1 cell line (<i>p</i> = 0.009 and 0.016, respectively). Inhibition of miR-155-5p partially restored BTLA protein expression in CLL patients (<i>p</i> = 0.01) and in MEC-1 cell lines (<i>p</i> = 0.058). Additionally, we aimed to evaluate the significance of BTLA deficiency in CLL cells on proliferation and IL-4 production of B cells. We found that secretion of IL-4 is not dependent on BTLA expression, since fractions of BTLA positive and BTLA negative B cells expressing intracellular IL-4 were similar in CLL patients and controls. We demonstrated that in controls the fraction of proliferating cells is lower in BTLA positive than in BTLA negative B cells (<i>p</i> = 0.059), which was not observed in CLL. However, the frequency of BTLA positive Ki67+ B cells in CLL was higher compared to corresponding cells from controls (<i>p</i> = 0.055) while there were no differences between the examined groups regarding frequency of BTLA negative Ki67+ B cells. Our studies suggest that miR-155-5p is involved in BTLA deficiency, affecting proliferation of CLL B cells, which may be one of the mechanisms responsible for CLL pathogenesis. |
| format |
article |
| author |
Lidia Karabon Anna Andrzejczak Lidia Ciszak Anna Tomkiewicz Aleksandra Szteblich Agnieszka Bojarska-Junak Jacek Roliński Dariusz Wołowiec Tomasz Wróbel Agata Kosmaczewska |
| author_facet |
Lidia Karabon Anna Andrzejczak Lidia Ciszak Anna Tomkiewicz Aleksandra Szteblich Agnieszka Bojarska-Junak Jacek Roliński Dariusz Wołowiec Tomasz Wróbel Agata Kosmaczewska |
| author_sort |
Lidia Karabon |
| title |
BTLA Expression in CLL: Epigenetic Regulation and Impact on CLL B Cell Proliferation and Ability to IL-4 Production |
| title_short |
BTLA Expression in CLL: Epigenetic Regulation and Impact on CLL B Cell Proliferation and Ability to IL-4 Production |
| title_full |
BTLA Expression in CLL: Epigenetic Regulation and Impact on CLL B Cell Proliferation and Ability to IL-4 Production |
| title_fullStr |
BTLA Expression in CLL: Epigenetic Regulation and Impact on CLL B Cell Proliferation and Ability to IL-4 Production |
| title_full_unstemmed |
BTLA Expression in CLL: Epigenetic Regulation and Impact on CLL B Cell Proliferation and Ability to IL-4 Production |
| title_sort |
btla expression in cll: epigenetic regulation and impact on cll b cell proliferation and ability to il-4 production |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/789b06c2e0d04cf591a5c197ecb1eab9 |
| work_keys_str_mv |
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