Dendritic and stromal cells from the spleen of lupic mice present phenotypic and functional abnormalities

Gleisner, María Alejandra; Reyes, Paz; Alfaro, Jennifer; Solanes, Paola; Simon, Valeska; Crisóstomo, Natalia; Sauma, Daniela; Rosemblatt, Mario; Bono, Marı́a Rosa

doi:10.1016/j.molimm.2013.01.011

Cited by 16 publications

(27 citation statements)

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“…Likewise, in human SLE [38], atrophic changes with lower volume and numbers of splenic corpuscles (lymphatic nodes or follicles) were also evidenced. These histological findings suggest that pristane-induced murine SLE model is more similar to human SLE than other commonly used models of this disease such as B/WF1 mice, in which only slight inflammatory cell infiltration [39] is observed.…”

Section: Discussionmentioning

confidence: 65%

CD4+CD69+ T cells and CD4+CD25+FoxP3+ Treg cells imbalance in peripheral blood, spleen and peritoneal lavage from pristane-induced systemic lupus erythematosus (SLE) mice

et al. 2019

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Background: Adaptive immune cells, including CD4 + CD69 + and CD4 + CD25 + FoxP3 + regulatory T (Treg) cells, are important for maintaining immunological tolerance. In human systemic lupus erythematosus (SLE), CD4 + CD25 + FoxP3 + Treg cells are reduced, whereas CD69 expression is increased, resulting in a homeostatic immune imbalance that may intensify autoreactive T cell activity. To analyze the mechanisms implicated in autotolerance failure, we evaluated CD4 + CD69 + and CD4 + CD25 + FoxP3 + T cells and interleukin profiles in a pristane-induced SLE experimental model. Methods: For lupus induction, 26 female Balb/c mice received a single intraperitoneal 0.5 ml dose of pristane, and 16 mice received the same dose of saline. Blood and spleen samples were collected from euthanized mice 90 and 120 days after pristane or saline inoculation. Mononuclear cells from peripheral blood (PBMC), peritoneal lavage (PL) and splenocytes were obtained by erythrocyte lysis and cryopreserved for further evaluation by flow cytometry using the GuavaEasyCyte TM HT. After thawing, cells were washed and stained with monoclonal antibodies against CD3, CD4, CD8, CD25, CD28, CD69, FoxP3, CD14 and Ly6C (BD Pharmingen TM). Interleukins were quantified using Multiplex® MAP. The Mann-Whitney test and the Pearson coefficient were used for statistical analysis, and p < 0.05 considered significant. Results: Compared with the controls, SLE-induced animals presented increased numbers of CD4 + CD69 + T cells in the blood on T90 and T120 (p = 0.022 and p = 0.008) and in the spleen on T120 (p = 0.049), but there were decreased numbers in the PL (p = 0.049) on T120. The percentage of Treg was lower in blood (p < 0.005 and p < 0.012) on T90 and T120, in spleen (p = 0.043) on T120 and in PL (p = 0.001) on T90. Increased numbers of CD4 + CD69+ T cells in the PL were positively associated with high IL-2 (p = 0.486) and IFN-γ (p = 0.017) levels, whereas reduced Treg cells in the blood were negatively correlated with TNFα levels (p = 0.043) and positively correlated with TGFβ1 (p = 0.038). Conclusion: Increased numbers of CD4 + CD69 + T cells and reduced numbers of CD4 + CD25 + FoxP3 + Treg cells with an altered interleukin profile suggests loss of autotolerance in pristane-induced lupus mice, which is similar to human lupus. Therefore, this model is useful in evaluating mechanisms of cellular activation, peripheral tolerance and homeostatic immune imbalance involved in human SLE.

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Section: Discussionmentioning

confidence: 65%

CD4+CD69+ T cells and CD4+CD25+FoxP3+ Treg cells imbalance in peripheral blood, spleen and peritoneal lavage from pristane-induced systemic lupus erythematosus (SLE) mice

et al. 2019

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“…Consistently, splenic and lymph node pDCs in lupic NZB/W F1 mice have also been shown to display elevated expression of costimulatory molecules, including CD40 and CD86 in pDCs when compared with mice prior to disease onset [41,42], suggesting that the BM-derived pDCs bear similarities to the peripheral circulating pDCs. Similarly, a recent report by Zhou et al has also demonstrated in disease NZB/W F1 mice a higher expression of MHC-II and CD80 in ex vivo splenic and BM pDCs when compared with pre-disease mice [30].…”

Section: Discussionmentioning

confidence: 89%

MicroRNA-155 Mediates Augmented CD40 Expression in Bone Marrow Derived Plasmacytoid Dendritic Cells in Symptomatic Lupus-Prone NZB/W F1 Mice

Yan

Yim

Tam

et al. 2016

IJMS

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Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease characterized by hyperactivated immune responses to self-antigens and persistent systemic inflammation. Previously, we reported abnormalities in circulating and bone marrow (BM)-derived plasmacytoid dendritic cells (pDCs) from SLE patients. Here, we aim to seek for potential regulators that mediate functional aberrations of pDCs in SLE. BM-derived pDCs from NZB/W F1 mice before and after the disease onset were compared for toll-like receptor (TLR) induced responses and microRNA profile changes. While pDCs derived from symptomatic mice were phenotypically comparable to pre-symptomatic ones, functionally they exhibited hypersensitivity to TLR7 but not TLR9 stimulation, as represented by the elevated upregulation of CD40, CD86 and MHC class II molecules upon R837 stimulation. Upregulated induction of miR-155 in symptomatic pDCs following TLR7 stimulation was observed. Transfection of miR-155 mimics in pre-symptomatic pDCs induced an augmented expression of Cd40, which is consistent with the increased CD40 expression in symptomatic pDCs. Overall, our results provide evidence for miR-155-mediated regulation in pDC functional abnormalities in SLE. Findings from this study contribute to a better understanding of SLE pathogenesis and ignite future interests in evaluating the molecular regulation in autoimmunity.

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“…Homing experiments demonstrate that DCs from lupusdiseased mice migrate preferentially to the spleen compared to DCs from control mice. This preferential recruitment and retention of DCs in the spleen are related to altered expression of different chemokine and chemokine receptors on both DCs and spleen stromal cells [16]. Recently, pDCs from spleen and bone marrow have been compared in several models of lupus-prone mice without clear results concerning the role of pDC in the development of lupus [17].…”

Section: Dendritic Cellsmentioning

confidence: 99%

“…In the NZB/W F1 lupus mice, spleen CD4 + T cells exhibit an activated phenotype characterized by high expression of PD-1, CD25, CD69 and increased secretion of IFN-γ and IL-10 [16,26]. The primary function of T cells in lupus is to help B cells in the production of autoantibodies [27], thus, avoiding the interaction between T and B cells may decrease the signs of the disease.…”

Section: T Cellsmentioning

confidence: 99%

A Spontaneous Mouse Model of Lupus: Physiology and Therapy

Tejón¹,

Hidalgo²,

Bono³

et al. 2020

Lupus - New Advances and Challenges

Self Cite

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Spontaneous models of lupus were recognized four decades ago beginning in the early 1960s with the NZB/NZW F1 (NZB/W F1) mouse, an F1 hybrid between the New Zealand Black (NZB) and New Zealand White (NZW) mice. Although the parental strains display limited autoimmunity, the NZB/W F1 develops severe lupuslike features similar to that of human lupus patients. Here, we will address the genetic characteristics of the model and discuss its main characteristics such as the presence of serum antinuclear autoantibodies (ANA) including anti-dsDNA, mild vasculitis, and the development of immune complex-mediated glomerulonephritis. Similar to human lupus, the disease develops primarily in female mice after six months of age, with a lesser percentage and severity in male mice. The relation of this phenomenon will be examined in the context of estrogen levels. The participation of both innate and adaptive immunity will be addressed as well as the contribution of both T and B cells in the development of the clinical aspects of the disease. We will focus on the use of the model as a valuable tool for elucidating the pathogenic mechanisms of the disease, as well as its use as preclinical testing of therapeutic for human use.

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Dendritic and stromal cells from the spleen of lupic mice present phenotypic and functional abnormalities

Cited by 16 publications

References 100 publications

CD4+CD69+ T cells and CD4+CD25+FoxP3+ Treg cells imbalance in peripheral blood, spleen and peritoneal lavage from pristane-induced systemic lupus erythematosus (SLE) mice

CD4+CD69+ T cells and CD4+CD25+FoxP3+ Treg cells imbalance in peripheral blood, spleen and peritoneal lavage from pristane-induced systemic lupus erythematosus (SLE) mice

MicroRNA-155 Mediates Augmented CD40 Expression in Bone Marrow Derived Plasmacytoid Dendritic Cells in Symptomatic Lupus-Prone NZB/W F1 Mice

A Spontaneous Mouse Model of Lupus: Physiology and Therapy

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