NDLI: Regulatory T cells contribute to the immunosuppressive phenotype of neutrophils in a mouse model of chronic lymphocytic leukemia

Content Provider	Springer Nature : BioMed Central
Author	Goral, Agnieszka Sledz, Marta Manda-Handzlik, Aneta Cieloch, Adrianna Wojciechowska, Alicja Lachota, Mieszko Mroczek, Agnieszka Demkow, Urszula Zagozdzon, Radoslaw Matusik, Katarzyna Wachowska, Malgorzata Muchowicz, Angelika
Abstract	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 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 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 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.
Related Links	https://ehoonline.biomedcentral.com/counter/pdf/10.1186/s40164-023-00452-9.pdf
Ending Page	16
Page Count	16
Starting Page	1
File Format	HTM / HTML
ISSN	21623619
DOI	10.1186/s40164-023-00452-9
Journal	Experimental Hematology & Oncology
Issue Number	1
Volume Number	12
Language	English
Publisher	BioMed Central
Publisher Date	2023-10-10
Access Restriction	Open
Subject Keyword	Hematology Oncology Cancer Research CD62L Chronic lymphocytic leukemia (CLL) Neutrophils Regulatory T cells (Treg) Immunosuppression
Content Type	Text
Resource Type	Article
Subject	Hematology Oncology Cancer Research
Journal Impact Factor	9.4/2023
5-Year Journal Impact Factor	8.3/2023

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