Carbon monoxide inhibits T cell activation in target organs during systemic lupus erythematosus

Abstract

SummarySystemic lupus erythematosus is characterized by the presence of circulating anti-nuclear antibodies (ANA) and systemic damage that includes nephritis, haematological manifestations and pulmonary compromise, among others. Although major progress has been made in elucidating the molecular mechanisms responsible for autoimmunity, current therapies for lupus have not improved considerably. Because the exposure of carbon monoxide (CO) has been shown to display beneficial immunoregulatory properties in different immune-mediated diseases, we investigated whether CO therapy improves lupus-related kidney injury in lupus mice. MRL-Fas lpr lupus mice were exposed to CO and disease progression was evaluated. ANA, leucocyteinfiltrating populations in spleen, kidney and lung and kidney lesions, were measured. CO therapy significantly decreased the frequency of activated B220 1 CD4 2 CD8 2 T cells in kidneys and lungs, as well as serum levels of ANA. Furthermore, we observed that CO therapy reduced kidney injury by decreasing proliferative glomerular damage and immune complexes deposition, decreased proinflammatory cytokine production and finally delayed the impairment of kidney function. CO exposure ameliorates kidney and lung leucocyte infiltration and delays kidney disease in MRLFas lpr lupus mice. Our data support the notion that CO could be explored as a potential new therapy for lupus nephritis.

The Cytoprotective Enzyme Heme Oxygenase-1 Suppresses Pseudorabies Virus Replication in vitro

“…CO is another metabolite of HO-1, which has been demonstrated to exert anti-inflammatory, antiapoptotic and cytoprotective effects in several types of diseases (Otterbein, 2002;Chung et al, 2008). CO has been reported to inhibit the expression of proinflammatory molecules on the cell surface (Riquelme et al, 2015a), regulation of mitochondrial function (Riquelme et al, 2015b) and inhibit T cell activation (Mackern-Oberti et al, 2015). With relevance to the present study, previous findings have reported an association between CO and viral replication in host cells.…”

Impact of Smoking Cigarette on the mRNA Expression of Cytokines in Mucosa of Inflammatory Bowel Disease

“…Carbon monoxide (CO) as a component of the gas phase of cigarette smoke is associated with anti-inflammatory properties. CO reduces antigen presentation by APCs and prevents the maturation of dendritic cells (DCs) (Sheikh et al 2011, Riquelme et al 2016, Mackern-Oberti et al 2015. CO-treated DCs retained the capacity to secrete anti-inflammatory cytokine IL-10 despite losing their ability to produce pro-inflammatory cytokine IL-12 (Riquelme et al 2016).…”

Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice

“…Interestingly, the HO‐1 expression is down‐regulated in monocytes isolated from patients with SLE and HO‐1 induction has been associated with disease amelioration in murine lupus . Finally, carbon monoxide, which is a product of HO‐1 enzymatic activity over heme group, decreases activated T‐cell numbers in kidneys and lungs, and decreases levels of anti‐nuclear antibodies (ANA) in lupus‐prone mice …”

“…21 Finally, carbon monoxide, which is a product of HO-1 enzymatic activity over heme group, decreases activated T-cell numbers in kidneys and lungs, and decreases levels of anti-nuclear antibodies (ANA) in lupus-prone mice. 22 In this study, we have evaluated the immunotherapeutic role of tolDCs generated by the HO-1 inductor cobalt (III) protoporphyrin IX (CoPP) in combination with two known tolerogenic drugs: dexamethasone (Dexa) and rosiglitazone (Rgz) in autoimmune mice. Given the background summarized above, tolDCs loaded with nuclear antigens, such as histones, arise as a promising self-antigen-specific therapy for SLE.…”