IL-10 restricts dendritic cell (DC) growth at the monocyte-to-monocyte-derived DC interface by disrupting anti-apoptotic and cytoprotective autophagic molecular machinery

Martin, Carla A.; Espaillat, Mel Pilar; Santiago‐Schwarz, Frances

doi:10.1007/s12026-015-8700-y

Cited by 9 publications

(7 citation statements)

References 55 publications

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“…These data suggest that activated B cells/plasma cells can promote the formation of CD11c+ cells in an IL-10 independent manner, at least in vitro . Though it is known that IL-10 inhibits cytoprotective mechanisms in monocyte derived DC leading to increased apoptosis (27), the mechanism of how activated B cells/plasma cells promote the generation of DC remains to be elucidated.…”

Section: Resultsmentioning

confidence: 99%

“…Similarly, this cytokine was shown to control monocyte differentiation to macrophages during peritoneal infection in mice (26). Moreover, IL-10 has been reported to restrict the growth of monocyte-derived DCs by the inhibition of cytoprotective autophagy leading to increased apoptosis (27). Several studies indicate that age-related changes in IL-10 production of various cell populations contribute to the age-related chronic progressive increase in the proinflammatory status, sometimes referred to as “inflammaging,” and changes of immune responses in older individuals (28–32).…”

Section: Introductionmentioning

confidence: 99%

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Bone Marrow Plasma Cells Modulate Local Myeloid-Lineage Differentiation via IL-10

et al. 2019

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Bone marrow plasma cells have been reported to represent a major source of IL-10; however, the impact of plasma cell derived IL-10 in that tissue remains poorly understood. We confirm in this study that even in the absence of acute immune reactions, mature plasma cells represent the dominant IL-10+ cell population in the bone marrow, and identify myeloid-lineage cells as a main local target for plasma cell derived IL-10. Using Vert-X IL-10 transcriptional reporter mice, we found that more than 50% of all IL-10+ cells in bone marrow were CD138+ plasma cells, while other IL-10+ B lineage cells were nearly absent in this organ. Accordingly, IL-10 was found in the supernatants of short-term cultures of FACS-sorted bone marrow plasma cells, confirming IL-10 secretion from these cells. IL-10+ bone marrow plasma cells showed a B220−/CD19−/MHCII low phenotype suggesting that these cells represent a mature differentiation stage. Approximately 5% of bone marrow leucocytes expressed the IL-10 receptor (IL-10R), most of them being CD115+/Ly6C+/CD11c− monocytes. Compared to littermate controls, young B lineage specific IL-10 KO mice showed increased numbers of CD115+ cells but normal populations of other myeloid cell types in bone marrow. However, at 7 months of age B lineage specific IL-10 KO mice exhibited increased populations of CD115+ myeloid and CD11c+ dendritic cells (DCs), and showed reduced F4/80 expression in this tissue; hence, indicating that bone marrow plasma cells modulate the differentiation of local myeloid lineage cells via IL-10, and that this effect increases with age. The effects of B cell/plasma cell derived IL-10 on the differentiation of CD115+, CD11c+, and F4/80+ myeloid cells were confirmed in co-culture experiments. Together, these data support the idea that IL-10 production is not limited to early plasma cell stages in peripheral tissues but is also an important feature of mature plasma cells in the bone marrow. Moreover, we provide evidence that already under homeostatic conditions in the absence of acute immune reactions, bone marrow plasma cells represent a non-redundant source for IL-10 that modulates local myeloid lineage differentiation. This is particularly relevant in older individuals.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bone Marrow Plasma Cells Modulate Local Myeloid-Lineage Differentiation via IL-10

et al. 2019

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“…During monocytes–DCs differentiation and DCs survival, cytoprotective autophagy responses are essential for counteracting IL-10-triggered apoptosis, but IL-10 can strongly inhibit starvation-induced autophagy and decrease Bcl-2 levels, which indicates increased levels of Beclin-1, LC3, and mature autophagosomes and results in restricting DCs growth. IL-10 not only kills nascent antigen-presenting DCs but also specifically skews the growth of DCs toward non-antigen-presenting monocytes–macrophages, and the autophagy inhibitor 3-methyladenine(3-MA) restricted DCs differentiation by prompting apoptosis [138] . Celastrol has been reported to ameliorate colitis in IL-10 deficient mice, which has clearly confirmed that celastrol up-regulated the autophagy of colon tissue in IL-10−/− mice by inhibiting the PI3K/Akt/mTOR signaling pathway.…”

Section: The Relationship Between Autophagy and Cytokinesmentioning

confidence: 99%

The relationship between autophagy and the immune system and its applications for tumor immunotherapy

et al. 2019

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Autophagy is a genetically well-controlled cellular process that is tightly controlled by a set of core genes, including the family of autophagy-related genes (ATG). Autophagy is a “double-edged sword” in tumors. It can promote or suppress tumor development, which depends on the cell and tissue types and the stages of tumor. At present, tumor immunotherapy is a promising treatment strategy against tumors. Recent studies have shown that autophagy significantly controls immune responses by modulating the functions of immune cells and the production of cytokines. Conversely, some cytokines and immune cells have a great effect on the function of autophagy. Therapies aiming at autophagy to enhance the immune responses and anti-tumor effects of immunotherapy have become the prospective strategy, with enhanced antigen presentation and higher sensitivity to CTLs. However, the induction of autophagy may also benefit tumor cells escape from immune surveillance and result in intrinsic resistance against anti-tumor immunotherapy. Increasing studies have proven the optimal use of either ATG inducers or inhibitors can restrain tumor growth and progression by enhancing anti-tumor immune responses and overcoming the anti-tumor immune resistance in combination with several immunotherapeutic strategies, indicating that induction or inhibition of autophagy might show us a prospective therapeutic strategy when combined with immunotherapy. In this article, the possible mechanisms of autophagy regulating immune system, and the potential applications of autophagy in tumor immunotherapy will be discussed.

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“…According to the present data, mice can recover because autophagy is involved in the phagocytosis of dead cells. Clearance of the apoptotic cells by phagocytes plays an important role in the maintenance of tissue homeostasis as well as the promotion of immunological tolerance and the antiinflammatory response [20,21]; however, the contribution of autophagic destruction of apoptotic cells by macrophages or other cells is not well defined.…”

Section: Discussionmentioning

confidence: 99%

Mouse Survival after 5- Fluorouracil treatment and the Role of Autophagic Clearance in Rapid Recovery

Marure

2021

CTOIJ

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Introduction: One of the most effective chemotherapeutic agents is 5-fluorouracil (5-FU). The aim of this study was to investigate its effects on bone marrow cell proliferation and autophagy in adult female C3H mice.Methods: C3H mice and bone marrow cells were exposed to 5-FU and its toxicity was evaluated mediating microscopic analysis, colonies formation, pH variations, apoptosis and autophagy.Results: After ablating bone marrow with 5-FU treatment, a rapid regeneration occurred during the subsequent 10 days. This was achieved by hematopoietic stem cells positive to autophagy/PI dye. Hence, the restoration of chemically depleted bone marrow was apparently initiated by cells normally resident in that tissue. We examined the recovery of colony formation by evaluating BFU-E, CFU-GM and CFU-GEMM. At 10 days post-administration of 5-FU, a full recovery of the formerly depopulated bone marrow was observed, with similar cell populations in treated and untreated mice. Bone marrow recovery is intrinsic to the hematopoietic progenitor cell compartment. Recovery was dependent on the autophagic cells that survived 5-FU ablation. Conclusion:A compartment of primitive stem cells exists in adult female C3H mice and suggest that these cells may have constituted the surviving population responsible for reconstituting the bone marrow after a single 5-FU treatment.

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IL-10 restricts dendritic cell (DC) growth at the monocyte-to-monocyte-derived DC interface by disrupting anti-apoptotic and cytoprotective autophagic molecular machinery

Cited by 9 publications

References 55 publications

Bone Marrow Plasma Cells Modulate Local Myeloid-Lineage Differentiation via IL-10

Bone Marrow Plasma Cells Modulate Local Myeloid-Lineage Differentiation via IL-10

The relationship between autophagy and the immune system and its applications for tumor immunotherapy

Mouse Survival after 5- Fluorouracil treatment and the Role of Autophagic Clearance in Rapid Recovery

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