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IL-10R expression in the bone marrow. Single cell suspensions from femurs and tibia of C57BL/6 mice were stained for IL-10R and CD115. (A) Representative flow cytometric staining for IL-10R compared to an isotype control (left). IL-10R+ cells were electronically gated and analyzed for the expression of CD115 (right). (B) IL-10R expression on gated CD115+ bone marrow monocytes. CD3+, B220+, and Gr-1+ cells were excluded from the analysis by electronic gating. Data represents results obtained from one of two independent experiments (n = 7). (C) Bone marrow dendritic cells (CD115+ Ly6C− CD11c+), neutrophils (CD115− Ly6C− CD11b+ Ly6G+), macrophages (CD115− CD11c− F4/80+), and monocytes (CD115+ Ly6C+ CD11c−) were sorted by FACS and IL-10RA expression was determined by real time PCR. Relative il10ra mRNA levels compared to actin are shown. Pooled data from two independent experiments are shown (n = 6).

IL-10R expression in the bone marrow. Single cell suspensions from femurs and tibia of C57BL/6 mice were stained for IL-10R and CD115. (A) Representative flow cytometric staining for IL-10R compared to an isotype control (left). IL-10R+ cells were electronically gated and analyzed for the expression of CD115 (right). (B) IL-10R expression on gated CD115+ bone marrow monocytes. CD3+, B220+, and Gr-1+ cells were excluded from the analysis by electronic gating. Data represents results obtained from one of two independent experiments (n = 7). (C) Bone marrow dendritic cells (CD115+ Ly6C− CD11c+), neutrophils (CD115− Ly6C− CD11b+ Ly6G+), macrophages (CD115− CD11c− F4/80+), and monocytes (CD115+ Ly6C+ CD11c−) were sorted by FACS and IL-10RA expression was determined by real time PCR. Relative il10ra mRNA levels compared to actin are shown. Pooled data from two independent experiments are shown (n = 6).

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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 m...

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... This underscores the potential of bmDCs to interpret and induce hematopoietic bias in response to immune stimuli. Considering the inherent challenges associated with G-CSF administration, such as the need for repeated injections and symptoms like bone pain, nausea, headache, and fatigue [70], the administration of in Long-lived plasma cells, identified as CD19 − /B220 − / MCH II lo CD138 + in mouse bone marrow, represent a substantial local source of IL-10 under steady-state conditions [97,98]. IL-10 assumes a pivotal role in regulating the proliferation and differentiation of myeloid cells, DCs, and macrophages within the bone marrow, operating in a nonredundant capacity [98,99]. ...
... Considering the inherent challenges associated with G-CSF administration, such as the need for repeated injections and symptoms like bone pain, nausea, headache, and fatigue [70], the administration of in Long-lived plasma cells, identified as CD19 − /B220 − / MCH II lo CD138 + in mouse bone marrow, represent a substantial local source of IL-10 under steady-state conditions [97,98]. IL-10 assumes a pivotal role in regulating the proliferation and differentiation of myeloid cells, DCs, and macrophages within the bone marrow, operating in a nonredundant capacity [98,99]. Myeloid-biased hematopoiesis increases in aged mice and the elderly [100], a phenomenon attributed to the age-related accumulation of plasma cells in the bone marrow. ...
... Diverging from the conventional independent differentiation pathway observed in regulatory T cells, Breg cell differentiation is contingent upon the immune environment in which they operate. Notably, flow cytometry analyses have revealed that under steadystate conditions, IL-10-producing cells constitute 0.1-0.2% of bone marrow cells, with 65% arising from plasma cells and 5% from B cells [98]. Consequently, Breg cells can emerge at different stages of B cell maturation, encompassing immature and mature B cell populations, accounting for the variable immunophenotypes observed in both murine and human contexts [111,112]. ...
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... Pro-inflammatory cytokines including interleukin (IL)-1β, IL-2, IL-6, as well as interferon gamma (IFN-γ) and tumour necrosis factor alpha (TNF-α), initiate and amplify the early-phase inflammatory events (Kany et al. 2019). Antiinflammatory cytokines such as IL-10 limit the effects of the pro-inflammatory agents and modulate the inflammatory processes (Meng et al. 2019). Regardless of the trigger stimulus, inflammation induces vasodilation, increases blood flow to the affected area, stimulates the release of further soluble factors that amplify the response, and increases blood vessel permeability, resulting in tissue swelling (Gusev and Zhuravleva 2022). ...
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... Moreover, PCs may indirectly increase cytokine levels, supporting their own survival through interaction with other immune cells: as specified above, they could induce IL-6 in DCs via CD28/CD80/CD86 (76). Aged PCs may even modulate myelopoiesis, reportedly in an IL-10-and TLR-dependent manner (158,159). This is relevant, since myeloid cells and progenitors are important producers of PC survival factors (71,73,74,87) and may provide a positive-feedback loop. ...
... Aside from the above, ASCs influence homeostatic processes such as hematopoiesis. 16,17 Although hematopoietic regulatory capacity has been ascribed to bone marrow (BM) ASCs, whether ASCs regulate hematopoietic processes in other organs such as the thymus (THY) remains to be determined. ...
... [9][10][11] In addition, this same secretory ability may influence their potential to regulate BM hematopoiesis. 16,17 As a result, understanding ASC biology is of growing importance as the repertoire of ASC functions seems to depend on the context in which ASCs exist. Along these lines, recent studies have utilized RNA-seq at both bulk 13,17,91,92 and single cell 56,93 levels in an attempt to define different ASC subsets or functional states. ...
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... TACI is an immune regulatory molecule that promotes the differentiation and survival of plasma cells [58]. Since plasma cells are a known source of IL-10 [59], enhanced TACI expression in WT dams may contribute to their enhanced IL-10 expression. Besides, expression of TACI by B1b cells was shown to be induced by TLR signaling and provided a heightened protective response [60]. ...
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... Under this context, a flow of CD45 + cells from the bone marrow to the systemic circulation, but not to the spleen, occurs. Among them, immature myeloid cells (Ly6C + CD11b + ) appear to exit the bone marrow and have been previously characterized [63,64]. We hypothesized that part of these cells is mobilized toward the spleen due to the enhanced presence of CXCL12 in this organ [38]. ...
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... The hallmark of the immune response durability is the formation of long-term memory immune cells including memory B and T lymphocytes and plasma cells. Apart from their known function at the forefront in secreting protective antibodies, plasma cells have recently been appreciated for their role in many biological functions through cytokines production [23][24][25][26][27][28]. Furthermore, although circulating antibodies are mainly produced by long-lived plasma cells, some reports suggest that short-lived plasmablasts could also persist and participate in maintaining antigen-specific circulating antibodies levels [29,30]. ...
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Background: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic zoonotic betacoronaviruses and a global public health concern. Better undersetting of the immune responses to MERS-CoV is needed to characterize the correlates of protection and durability of the immunity and to aid in developing preventative and therapeutic interventions. While MERS-CoV-specific circulating antibodies could persist for several years post-recovery, their waning raises concerns about their durability and role in protection. Nonetheless, memory B and T cells could provide long-lasting protective immunity despite the serum antibodies levels. Methods: Serological and flow cytometric analysis of MERS-CoV-specific immune responses were performed on samples collected from a cohort of recovered individuals who required intensive care unit (ICU) admission as well as hospital or home isolation several years after infection to characterize the longevity and quality of humoral and cellular immune responses. Results: Our data showed that MERS-CoV infection could elicit robust long-lasting virus-specific binding and neutralizing antibodies as well as T and B cell responses up to 6.9 years post-infection regardless of disease severity or need for ICU admission. Apart from the persistent high antibody titers, this response was characterized by B cell subsets with antibody-independent functions as demonstrated by their ability to produce TNF-α, IL-6, and IFN-γ cytokines in response to antigen stimulation. Furthermore, virus-specific activation of memory CD8+ and CD4+ T cell subsets from MERS-recovered patients resulted in secretion of high levels of TNF-α, IL-17 and IFN-γ. Conclusions: MERS-CoV infection could elicit robust long-lasting virus-specific humoral and cellular responses.
... Under this context, a flow of CD45 + cells from the bone marrow to systemic circulation, but not to the spleen, occurs. Among them, immature myeloid cells (Ly6C + CD11b + ) appear to exit the bone marrow and have been previously characterized (57,58). We hypothesized that part of these cells are mobilized towards the spleen due to the enhanced presence of CXCL12 in this organ (34). ...
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In the course of atherogenesis, the spleen plays an important role in the regulation of extramedullary hematopoiesis and in the control of circulating immune cells, which contributes to plaque progression. Here, we have investigated the role of splenic nucleotide-binding oligomerization domain 1 (NOD1) in the recruitment of circulating immune cells as well as the involvement of this immune organ in extramedullary hematopoiesis in mice fed a high-fat high-cholesterol diet (HFD). Under HFD conditions, the absence of NOD1 enhances the mobilization of immune cells, mainly neutrophils, from the bone marrow to the blood. To determine the effect of NOD1-dependent mobilization of immune cells under pro-atherogenic conditions, Apoe -/- and Apoe -/- Nod1 -/- mice fed HFD for 4 weeks were used. Splenic NOD1 from Apoe -/- mice was activated after feeding HFD as inferred by the phosphorylation of the NOD1 downstream targets RIPK2 and TAK1. Moreover, this activation was accompanied by the release of neutrophil extracellular traps (NETs), as determined by the increase in the expression of peptidyl arginine deiminase 4, and the identification of citrullinated histone H3 in this organ. This formation of NETs was significantly reduced in Apoe -/- Nod1 -/- mice. Indeed, the presence of Ly6G + cells and the lipidic content in the spleen of mice deficient in Apoe and Nod1 was reduced when compared to the Apoe -/- counterparts, which suggests that the mobilization and activation of circulating immune cells is altered in the absence of NOD1. Furthermore, confirming previous studies, Apoe -/- Nod1 -/- mice showed a reduced atherogenic disease and a diminished recruitment of neutrophils in the spleen, compared to Apoe -/- mice. However, splenic artery-ligation reduced the atherogenic burden in Apoe -/- mice an effect that, unexpectedly was lost in Apoe -/- Nod1 -/- mice. Together, these results suggest that neutrophil accumulation and activity in the spleen is driven in part by NOD1 activation in mice fed HFD, contributing in this way to regulate atherogenic progression.