Regulatory T cells contribute to the immunosuppressive phenotype of neutrophils in a mouse model of chronic lymphocytic leukemia.
CD62L
Chronic lymphocytic leukemia (CLL)
Immunosuppression
Neutrophils
Regulatory T cells (Treg)
Journal
Experimental hematology & oncology
ISSN: 2162-3619
Titre abrégé: Exp Hematol Oncol
Pays: England
ID NLM: 101590676
Informations de publication
Date de publication:
10 Oct 2023
10 Oct 2023
Historique:
received:
07
04
2023
accepted:
29
09
2023
medline:
11
10
2023
pubmed:
11
10
2023
entrez:
11
10
2023
Statut:
epublish
Résumé
Impaired neutrophil activity is an important issue in chronic lymphocytic leukemia (CLL), as it contributes to a dysfunctional immune response leading to life-threatening infections in patients. Some features typical of CLL neutrophils, e.g., the B-cell-supportive secretion profile, have already been described. However, most of these studies were performed on cells isolated from peripheral blood. It is still unclear which molecular factors and cell types are involved in shaping neutrophil function and phenotype in the CLL microenvironment. Since regulatory T cells (Treg) play an important role in CLL progression and influence the activity of neutrophils, we investigated the crosstalk between Treg and neutrophils in the spleen using a murine model of CLL. In this work, we used an Eµ-TCL1 mouse model of human CLL. For our in vivo and ex vivo experiments, we inoculated wild-type mice with TCL1 leukemic cells isolated from Eµ-TCL1 transgenic mice and then monitored disease progression by detecting leukemic cells in peripheral blood. We analyzed both the phenotype and activity of neutrophils isolated from the spleens of TCL1 leukemia-bearing mice. To investigate the interrelation between Treg and neutrophils in the leukemia microenvironment, we performed experiments using TCL1-injected DEREG mice with Treg depletion or RAG2KO mice with adoptively transferred TCL1 cells alone or together with Treg. The obtained results underline the plasticity of the neutrophil phenotype, observed under the influence of leukemic cells alone and depending on the presence of Treg. In particular, Treg affect the expression of CD62L and IL-4 receptor in neutrophils, both of which are crucial for the function of these cells. Additionally, we show that Treg depletion and IL-10 neutralization induce changes in the leukemia microenvironment, partially restoring the "healthy" phenotype of neutrophils. Altogether, the results indicate that the crosstalk between Treg and neutrophils in CLL may play an important role in CLL progression by interfering with the immune response.
Sections du résumé
BACKGROUND
BACKGROUND
Impaired neutrophil activity is an important issue in chronic lymphocytic leukemia (CLL), as it contributes to a dysfunctional immune response leading to life-threatening infections in patients. Some features typical of CLL neutrophils, e.g., the B-cell-supportive secretion profile, have already been described. However, most of these studies were performed on cells isolated from peripheral blood. It is still unclear which molecular factors and cell types are involved in shaping neutrophil function and phenotype in the CLL microenvironment. Since regulatory T cells (Treg) play an important role in CLL progression and influence the activity of neutrophils, we investigated the crosstalk between Treg and neutrophils in the spleen using a murine model of CLL.
METHODS
METHODS
In this work, we used an Eµ-TCL1 mouse model of human CLL. For our in vivo and ex vivo experiments, we inoculated wild-type mice with TCL1 leukemic cells isolated from Eµ-TCL1 transgenic mice and then monitored disease progression by detecting leukemic cells in peripheral blood. We analyzed both the phenotype and activity of neutrophils isolated from the spleens of TCL1 leukemia-bearing mice. To investigate the interrelation between Treg and neutrophils in the leukemia microenvironment, we performed experiments using TCL1-injected DEREG mice with Treg depletion or RAG2KO mice with adoptively transferred TCL1 cells alone or together with Treg.
RESULTS
RESULTS
The obtained results underline the plasticity of the neutrophil phenotype, observed under the influence of leukemic cells alone and depending on the presence of Treg. In particular, Treg affect the expression of CD62L and IL-4 receptor in neutrophils, both of which are crucial for the function of these cells. Additionally, we show that Treg depletion and IL-10 neutralization induce changes in the leukemia microenvironment, partially restoring the "healthy" phenotype of neutrophils.
CONCLUSIONS
CONCLUSIONS
Altogether, the results indicate that the crosstalk between Treg and neutrophils in CLL may play an important role in CLL progression by interfering with the immune response.
Identifiants
pubmed: 37817276
doi: 10.1186/s40164-023-00452-9
pii: 10.1186/s40164-023-00452-9
pmc: PMC10563345
doi:
Types de publication
Journal Article
Langues
eng
Pagination
89Subventions
Organisme : The Polish National Science Centre
ID : 2018/29/B/NZ6/01962
Informations de copyright
© 2023. YUMED Inc. and BioMed Central Ltd.
Références
Eur J Immunol. 2011 Feb;41(2):306-12
pubmed: 21268001
J Leukoc Biol. 2015 Oct;98(4):489-96
pubmed: 25632045
J Inflamm Res. 2021 Jan 20;14:141-162
pubmed: 33505167
Int J Mol Sci. 2021 Dec 29;23(1):
pubmed: 35008790
Infect Immun. 2012 Jan;80(1):159-68
pubmed: 22038918
Int J Mol Sci. 2020 Mar 06;21(5):
pubmed: 32155826
J Hematol Oncol. 2022 Aug 28;15(1):118
pubmed: 36031601
Immunology. 2010 Dec;131(4):583-92
pubmed: 20722759
Exp Mol Med. 2007 Aug 31;39(4):439-49
pubmed: 17934331
Blood. 2016 Nov 10;128(19):2327-2337
pubmed: 27609642
J Leukoc Biol. 2007 May;81(5):1287-96
pubmed: 17264307
Cancers (Basel). 2021 Apr 15;13(8):
pubmed: 33920868
Int J Cancer. 2019 Mar 1;144(5):1128-1134
pubmed: 30178523
Immunobiology. 2013 Apr;218(4):455-64
pubmed: 22749980
Sci Adv. 2021 Sep 10;7(37):eabj2101
pubmed: 34516771
Front Immunol. 2022 May 25;13:836754
pubmed: 35693822
Oncotarget. 2017 Aug 8;8(49):84889-84901
pubmed: 29156691
Proc Natl Acad Sci U S A. 2002 May 14;99(10):6955-60
pubmed: 12011454
Front Oncol. 2020 Aug 19;10:1422
pubmed: 32974152
J Allergy Clin Immunol. 2019 Jul;144(1):267-279.e4
pubmed: 30768990
J Hematol Oncol. 2020 Dec 10;13(1):171
pubmed: 33302977
Nat Rev Cancer. 2020 Sep;20(9):485-503
pubmed: 32694624
Oncotarget. 2016 Oct 11;7(41):67333-67346
pubmed: 27637084
Eur J Immunol. 2022 Mar;52(3):484-502
pubmed: 34870329
Leukemia. 2021 Nov;35(11):3188-3200
pubmed: 33731852
Cancer. 2015 Sep 1;121(17):2883-91
pubmed: 25931291
Blood. 2017 Jun 29;129(26):3476-3485
pubmed: 28515092
Front Immunol. 2019 Apr 09;10:680
pubmed: 31024539
Front Immunol. 2020 Oct 29;11:593610
pubmed: 33193442
Blood Adv. 2021 Mar 9;5(5):1259-1272
pubmed: 33651101
Nat Rev Cancer. 2021 Jul;21(7):412
pubmed: 34089012
Eur J Immunol. 2010 Sep;40(9):2360-8
pubmed: 20549669
Cancer Res. 2016 Sep 15;76(18):5253-65
pubmed: 27488528
Cell Rep. 2016 Feb 23;14(7):1748-1760
pubmed: 26876171
Cancer Metastasis Rev. 2021 Mar;40(1):221-244
pubmed: 33438104
Front Immunol. 2022 Feb 28;13:781364
pubmed: 35296093
J Exp Med. 2013 Jul 1;210(7):1283-99
pubmed: 23825232
J Exp Clin Cancer Res. 2015 Nov 18;34:141
pubmed: 26581194
Gut. 2017 Nov;66(11):1900-1911
pubmed: 28274999
Nat Med. 2022 Jan;28(1):201-211
pubmed: 34782790
Cell Death Dis. 2016 Jan 28;7:e2071
pubmed: 26821067
Leukemia. 2020 Aug;34(8):2012-2024
pubmed: 32457353
Nat Commun. 2020 Jun 2;11(1):2762
pubmed: 32488020
J Hematol Oncol. 2022 May 18;15(1):61
pubmed: 35585567
Immunity. 2016 Jul 19;45(1):172-84
pubmed: 27438770
Immunol Cell Biol. 2019 Mar;97(3):289-298
pubmed: 30710448
ACS Nano. 2021 Nov 23;15(11):17515-17527
pubmed: 34709030
J Immunol. 2017 Aug 1;199(3):1086-1095
pubmed: 28659355
Blood. 2006 Aug 15;108(4):1334-8
pubmed: 16670263
Blood. 2019 May 16;133(20):2159-2167
pubmed: 30898857
Eur J Haematol. 1996 Jul;57(1):46-53
pubmed: 8698131