Alpha 1 Antitrypsin Inhibits Dendritic Cell Activation and Attenuates Nephritis in a Mouse Model of Lupus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution and considerable mortality and morbidity. Although the pathogenesis of this disease remains elusive, over-reactive dendritic cells (DCs) play a critical role in the disease development. It has been shown that human alpha-1 antitrypsin (hAAT) has protective effects in type 1 diabetes and rheumatoid arthritis mouse models. In the present study, we tested the effect of AAT on DC differentiation and functions, as well as its protective effect in a lupus-prone mouse model. We showed that hAAT treatment significantly inhibited LPS (TLR4 agonist) and CpG (TLR9 agonist) -induced bone-marrow (BM)-derived conventional and plasmacytoid DC (cDC and pDC) activation and reduced the production of inflammatory cytokines including IFN-I, TNF-α and IL-1β. In MRL/lpr mice, hAAT treatment significantly reduced BM-derived DC differentiation, serum autoantibody levels, and importantly attenuated renal pathology. Our results for the first time demonstrate that hAAT inhibits DC activation and function, and it also attenuates autoimmunity and renal damage in the MRL/lpr lupus model. These results imply that hAAT has a therapeutic potential for the treatment of SLE in humans.

Exploration ofα1-Antitrypsin Treatment Protocol for Islet Transplantation: Dosing Plan and Route of Administration

“…However, preclinical data suggest that AAT treatment may benefit conditions outside AATD, including transplant rejection, as well as ischemia-reperfusion injury, collagen-induced arthritis, graft-versus-host disease, experimental autoimmune encephalomyelitis, lupus, and preeclampsia (Daemen et al, 2000; Lewis et al, 2005; Lewis et al, 2008a; Grimstein et al, 2010; Subramanian et al, 2011; Tawara et al, 2012; Gao et al, 2014; Feng et al, 2015; Elshikha et al, 2016; Feng et al, 2016). AAT displays particular benefit in the case of inflamed pancreatic islets both in vitro and in vivo, as reviewed in Fleixo-Lima et al (2014).…”

Causes and Outcomes of Hospitalization among Systemic Lupus Erythematosus Patients in Aseer Central Hospital, Saudi Arabia : A Retrospective Study

“…Regarding the distribution of hospital admissions in relation to patients' characteristics, Table (1) shows that the overall admission rate was around two times and the highest admissions were recorded for those whose age was 40 years or more, compared to those who were below 20 years (1.97 vs. 1.54 times, respectively) (P= 0.097). The average number of admissions for females was higher than males (1.63 and 1.38) (P= 0.391), while the average of admission times for those who had the disease for more than 10 years was about 1.82 times which is higher than those who had the disease for 2 years or less (1.19 times) (P= 0.001).…”

“…Systemic lupus erythematosus (SLE) is a worldwide autoimmune disorder with significant morbidity and mortality 1 . It is a persistent longterm disorder which is more common in women [2][3] .…”

“…It is a persistent longterm disorder which is more common in women [2][3] . The underlying cause of autoimmune diseases is not fully understood, but the hidden process in SLE is that the immune system mistakenly attacks healthy tissues by using complexes or cytotoxic antibodies which impact on body organs 1,4 . Therefore, SLE has unevenness at onset that renders correct and early diagnosis quite challenging 5 .…”

Anti‐inflammaging effects of human alpha‐1 antitrypsin

“…However, it is challenging to control the progress of inflammaging. In several animal models of inflammation related diseases, hAAT has been shown to have remarkable effect on delaying or blocking the onset of diseases or alleviating the symptoms (Ma et al ., 2010; Cao et al ., 2011; Grimstein et al ., 2011; Moldthan et al ., 2014; Akbar et al ., 2016; Elshikha et al ., 2016). In fact, some of them are age‐associated diseases, such as arthritis and osteoporosis.…”