Haem oxygenase 1 expression is altered in monocytes from patients with systemic lupus erythematosus

Herrada, Andrés A.; Llanos, Carolina; Mackern-Oberti, Juan Pablo; Carreño, Leandro J.; Henríquez, Carla; Gómez, Roberto; Gutiérrez, Miguel; Anegón, Ignacio; Jacobelli, S; Kalergis, Alexis M.

doi:10.1111/j.1365-2567.2012.03598.x

Cited by 35 publications

(32 citation statements)

References 58 publications

(103 reference statements)

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“…Splenocytes from HO‐1 KO mice also showed an augmented secretion of pro‐inflammatory cytokines, such as interleukin‐1 (IL‐1), IL‐6 and tumour necrosis factor‐ α . Consistent with these observations, monocytes from patients suffering from the autoimmune disease systemic lupus erythematosus, which manifests as exacerbated general inflammation, showed a reduced expression of HO‐1 . Similar results were seen in patients with multiple sclerosis, who displayed reduced levels of HO‐1 in peripheral blood mononuclear cells during disease exacerbation .…”

Section: Biological Function Of Ho‐1 Activitysupporting

confidence: 78%

Modulation of antigen processing by haem‐oxygenase 1. Implications on inflammation and tolerance

et al. 2016

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SummaryHaem-oxygenase-1 (HO-1) is an enzyme responsible for the degradation of haem that can suppress inflammation, through the production of carbon monoxide (CO). It has been shown in several experimental models that genetic and pharmacological induction of HO-1, as well as non-toxic administration of CO, can reduce inflammatory diseases, such as endotoxic shock, type 1 diabetes and graft rejection. Recently, it was shown that the HO-1/CO system can alter the function of antigen-presenting cells (APCs) and reduce T-cell priming, which can be beneficial during immune-driven inflammatory diseases. The molecular mechanisms by which the HO-1 and CO reduce both APC-and T-cell-driven immunity are just beginning to be elucidated. In this article we discuss recent findings related to the immune regulatory capacity of HO-1 and CO at the level of recognition of pathogen-associated molecular patterns and T-cell priming by APCs. Finally, we propose a possible regulatory role for HO-1 and CO over the recently described mitochondria-dependent immunity. These concepts could contribute to the design of new therapeutic tools for inflammation-based diseases.

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Section: Biological Function Of Ho‐1 Activitysupporting

confidence: 78%

Modulation of antigen processing by haem‐oxygenase 1. Implications on inflammation and tolerance

et al. 2016

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“…These observations suggest that it is probably the reduction of immunogenic signals, instead of the up‐regulation of suppressive molecules, that is the key to achieving a tolerogenic DC phenotype. Although monocytes from patients with SLE have abnormal properties, our results suggest that functional tolDCs can be obtained from them and autologous immunotherapy for SLE may in fact be plausible, even with the described particular characteristics of this cell type in patients with SLE …”

Section: Discussionmentioning

confidence: 78%

Autologous tolerogenic dendritic cells derived from monocytes of systemic lupus erythematosus patients and healthy donors show a stable and immunosuppressive phenotype

et al. 2017

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Systemic lupus erythematosus (SLE) is an autoimmune disease with unrestrained T-cell and B-cell activity towards self-antigens. Evidence shows that apoptotic cells (ApoCells) trigger an autoreactive response against nuclear antigens in susceptible individuals. In this study, we focus on generating and characterizing tolerogenic dendritic cells (tolDCs) to restore tolerance to ApoCells. Monocyte-derived dendritic cells (DCs) from healthy controls and patients with SLE were treated with dexamethasone and rosiglitazone to induce tolDCs. Autologous apoptotic lymphocytes generated by UV irradiation were given to tolDCs as a source of self-antigens. Lipopolysaccharide (LPS) was used as a maturation stimulus to induce the expression of co-stimulatory molecules and secretion of cytokines. TolDCs generated from patients with SLE showed a reduced expression of co-stimulatory molecules after LPS stimulation compared with mature DCs. The same phenomenon was observed in tolDCs treated with ApoCells and LPS. In addition, ApoCell-loaded tolDCs stimulated with LPS secreted lower levels of interleukin-6 (IL-6) and IL-12p70 than mature DCs without differences in IL-10 secretion. The functionality of tolDCs was assessed by their capacity to prime allogeneic T cells. TolDCs displayed suppressor properties as demonstrated by a significantly reduced capacity to induce allogeneic T-cell proliferation and activation. ApoCell-loaded tolDCs generated from SLE monocytes have a stable immature/tolerogenic phenotype that can modulate CD4 T-cell activation. These properties make them suitable for an antigen-specific immunotherapy for SLE.

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“…In addition to the increased expression of co‐stimulatory molecules, myeloid cells from SLE patients show reduced expression of the anti‐inflammatory enzyme HO‐1 . Here, we evaluate whether HO‐1 induction in combination with Dexa and Rgz generates an improved tolerogenic profile.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, it has been demonstrated that treatment with Dexa blocks DC maturation and it has been previously used together with Rgz, which is a known nuclear factor‐ κ B inhibitor . HO‐1 is a critical enzyme involved in renal protection and its expression is reduced in SLE patients . Induction of this enzyme has been related to amelioration in lupus‐prone mice .…”

Section: Discussionmentioning

confidence: 99%

Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice

et al. 2019

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Summary Current treatments for systemic autoimmune diseases partially improve the health of patients displaying low pharmacological efficacy and systemic immunosuppression. Here, the therapeutic potential of transferring tolerogenic dendritic cells (tolDCs) generated with heme‐oxygenase inductor cobalt (III) protoporphyrin IX (CoPP), dexamethasone and rosiglitazone for the treatment of systemic autoimmunity was evaluated in two murine models of systemic lupus erythematosus (SLE), MRL‐Faslpr and NZM2410 mice. Dendritic cells treated ex vivo with these drugs showed a stable tolerogenic profile after lipopolysaccharide stimulation. Regular doses of tolDCs were administered to anti‐nuclear antibody‐positive mice throughout 60–70 days, and the clinical score was evaluated. Long‐term treatment with these tolDCs was well tolerated and effective to improve the clinical score on MRL‐Faslpr lupus‐prone mice. Additionally, decreased levels of anti‐nuclear antibodies in NZM2410 mice were observed. Although tolDC treatment increased regulatory T cells, no significant reduction of renal damage or glomerulonephritis could be found. In conclusion, these results suggest that the transfer of histone‐loaded tolDCs could improve only some SLE symptoms and reduced anti‐nuclear antibodies. This is the first study to evaluate antigen‐specific tolDC administration to treat SLE. Our report strengthens the clinical relevance of tolDC generation with CoPP, dexamethasone and rosiglitazone and the use of these modified cells as a therapy for systemic autoimmunity.

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Haem oxygenase 1 expression is altered in monocytes from patients with systemic lupus erythematosus

Cited by 35 publications

References 58 publications

Modulation of antigen processing by haem‐oxygenase 1. Implications on inflammation and tolerance

Modulation of antigen processing by haem‐oxygenase 1. Implications on inflammation and tolerance

Autologous tolerogenic dendritic cells derived from monocytes of systemic lupus erythematosus patients and healthy donors show a stable and immunosuppressive phenotype

Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice

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