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IL-10 Rescues CLL Survival through Repolarization of Inflammatory Nurse-like Cells.

ABSTRACT: Tumor-associated macrophages (TAMs) in chronic lymphocytic leukemia (CLL) are also called nurse-like cells (NLC), and confer survival signals through the release of soluble factors and cellular contacts. While in most patient samples the presence of NLC in co-cultures guarantees high viability of leukemic cells in vitro, in some cases this protective effect is absent. These macrophages are characterized by an "M1-like phenotype". We show here that their reprogramming towards an M2-like phenotype (tumor-supportive) with IL-10 leads to an increase in leukemic cell survival. Inflammatory cytokines, such as TNF, are also able to depolarize M2-type protective NLC (decreasing CLL cell viability), an effect which is countered by IL-10 or blocking antibodies. Interestingly, both IL-10 and TNF are implied in the pathophysiology of CLL and their elevated level is associated with bad prognosis. We propose that the molecular balance between these two cytokines in CLL niches plays an important role in the maintenance of the protective phenotype of NLCs, and therefore in the survival of CLL cells.

SUBMITTER: Domagala M

PROVIDER: S-EPMC8750769 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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IL-10 Rescues CLL Survival through Repolarization of Inflammatory Nurse-like Cells.

Domagala Marcin M Ysebaert Loïc L Ligat Laetitia L Lopez Frederic F Fournié Jean-Jacques JJ Laurent Camille C Poupot Mary M

Cancers 20211221 1

Tumor-associated macrophages (TAMs) in chronic lymphocytic leukemia (CLL) are also called nurse-like cells (NLC), and confer survival signals through the release of soluble factors and cellular contacts. While in most patient samples the presence of NLC in co-cultures guarantees high viability of leukemic cells in vitro, in some cases this protective effect is absent. These macrophages are characterized by an "M1-like phenotype". We show here that their reprogramming towards an M2-like phenotype ...[more]

PMID: 35008174

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Project description:BackgroundMajor depressive disorder is a widespread mood disorder. One of the most debilitating symptoms patients often experience is cognitive impairment. Recent findings suggest that inflammation is associated with depression and impaired cognition. Pro-inflammatory cytokines are elevated in the blood of depressed patients and impair learning and memory processes, suggesting that an anti-inflammatory approach might be beneficial for both depression and cognition.MethodsWe subjected mice to the learned helplessness paradigm and evaluated novel object recognition and spatial memory. Mice were treated with IL-10 intranasally or/and microglia cells were depleted using PLX5622. Statistical differences were tested using ANOVA or t tests.ResultsWe first established a mouse model of depression in which learning and memory are impaired. We found that learned helplessness (LH) impairs novel object recognition (NOR) and spatial working memory. LH mice also exhibit reduced hippocampal dendritic spine density and increased microglial activation compared to non-shocked (NS) mice or mice that were subjected to the learned helpless paradigm but did not exhibit learned helplessness (non-learned helpless or NLH). These effects are mediated by microglia, as treatment with PLX5622, which depletes microglia, restores learning and memory and hippocampal dendritic spine density in LH mice. However, PLX5622 also impairs learning and memory and reduces hippocampal dendritic spine density in NLH mice, suggesting that microglia in NLH mice produce molecules that promote learning and memory. We found that microglial interleukin (IL)-10 levels are reduced in LH mice, and IL-10 administration is sufficient to restore NOR, spatial working memory, and hippocampal dendritic spine density in LH mice, and in NLH mice treated with PLX5622 consistent with a pro-cognitive role for IL-10.ConclusionsAltogether these data demonstrate the critical role of IL-10 in promoting learning and memory after learned helplessness.

Dataset Information

IL-10 Rescues CLL Survival through Repolarization of Inflammatory Nurse-like Cells.

Publications

IL-10 Rescues CLL Survival through Repolarization of Inflammatory Nurse-like Cells.

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