Estrogen Receptor α Deficiency Modulates TLR Ligand–Mediated PDC-TREM Expression in Plasmacytoid Dendritic Cells in Lupus-Prone Mice

Scott, Jennifer; Cunningham, Melissa A.; Naga, Osama; Wirth, Jena R.; Eudaly, Jackie; Gilkeson, Gary S.

doi:10.4049/jimmunol.1500315

Cited by 12 publications

(18 citation statements)

References 39 publications

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“…Increasing evidence indicates that dendritic cells (DCs) play critical roles in the development of SLE [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. DCs are activated by immune complexes and act as a bridge between the innate and adaptive immune responses [ 10 ]. DCs express Fc receptors, through which immune complexes can bind and internalize [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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

Elshikha

Chen

et al. 2016

PLoS ONE

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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.

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Section: Introductionmentioning

confidence: 99%

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

Elshikha

Chen

et al. 2016

PLoS ONE

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“…In the NZM2410 lupus murine model, the ER-a deficiency decreased IFN-a production by pDCs from spleen, which is accompanied by a lower disease severity (Scott et al 2015) (Fig. 2).…”

Section: Role Of E/er-a Pathway On Ifn Signaturementioning

confidence: 94%

“…However, in the NZB/W F1 female experimental model, ER deficiency did not prevent lymphoproliferation and splenomegaly suggesting that proliferation of lymphoid cells could be separated from loss of tolerance and in which E2 may promote autoreactive responses (Bynote et al 2008). Interestingly, in the NZM2410 lupus murine model, the ER-a deficiency decreased the expression of MHC II and PDC-TREM receptor by pDCs from spleen showing that E2/ER-a signaling plays a crucial role in T cell priming (Scott et al 2015) (Fig. 2).…”

Section: Modulation Of DC Function By Steroids and Prl During Sle E2/mentioning

confidence: 96%

“…Although extensive work has been done using lupus murine models deficient in hormones receptors or pharmacologic approaches, still it has not been defined if hormones/hormone receptors expressed on cDCs and/or pDCs contribute to lupus pathogenesis and progression. Interestingly, it was demonstrated that E2 promotes the development of systemic autoimmunity in different lupus murine models (MRL/lpr, B6.Sle1, NZB/W F1 and NZM2410), and that the loss of ER-a in these mice models decreases immune cell activation and disease activity (Bynote et al 2008;Scott et al 2015;Yoachim et al 2015). However, in the NZB/W F1 female experimental model, ER deficiency did not prevent lymphoproliferation and splenomegaly suggesting that proliferation of lymphoid cells could be separated from loss of tolerance and in which E2 may promote autoreactive responses (Bynote et al 2008).…”

Section: Modulation Of DC Function By Steroids and Prl During Sle E2/mentioning

confidence: 99%

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Hormonal Modulation of Dendritic Cells Differentiation, Maturation and Function: Implications for the Initiation and Progress of Systemic Autoimmunity

Mackern-Oberti

Jara

Riedel

et al. 2016

Arch. Immunol. Ther. Exp.

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Hormonal homeostasis is crucial for keeping a competent and healthy immune function. Several hormones can modulate the function of various immune cells such as dendritic cells (DCs) by influencing the initiation of the immune response and the maintenance of peripheral tolerance to self-antigens. Hormones, such as estrogens, prolactin, progesterone and glucocorticoids may profoundly affect DCs differentiation, maturation and function leading to either a pro-inflammatory or an anti-inflammatory (or tolerogenic) phenotype. If not properly regulated, these processes can contribute to the pathogenesis of autoimmune disease. An unbalanced hormonal status may affect the production of pro-inflammatory cytokines, the expression of activating/inhibitory receptors and co-stimulatory molecules on conventional and plasmacytoid DCs (pDCs), conferring susceptibility to develop autoimmunity. Estrogen receptor (ER)-α signaling in conventional DCs can promote IFN-α and IL-6 production and induce the expression of CD40, CD86 and MHCII molecules. Furthermore, estrogen modulates the pDCs response to Toll-like receptor ligands enhancing T cell priming. During lupus pathogenesis, ER-α deficiency decreased the expression of MHC II on pDCs from the spleen. In contrast, estradiol administration to lupus-prone female mice increased the expression of co-stimulatory molecules, enhanced the immunogenicity and produced large amounts of IL-6, IL-12 and TNF-α by bone marrow-derived DCs. These data suggest that estradiol/ER signaling may play an active role during lupus pathology. Similarly, understanding hormonal modulation of DCs may favor the design of new therapeutic strategies based on autologous tolerogenic DCs transfer, especially in sex-biased systemic autoimmune diseases. In this review, we discuss recent data relative to the role of different hormones (estrogen, prolactin, progesterone and glucocorticoids) in DC function during systemic autoimmune pathogenesis.

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“…Activating the dendritic cells' ERs also appears to have a role in DC differentiation [182]. In a mouse model for lupus, ER was demonstrated to modulate plasmacytoid dendritic cell function and interferon activity [183]. In another model (C57BL/10.Q mice) [184], plasma estrogen levels may also have contributed to the recruitment of innate immune cells towards inflammatory sites.…”

Section: Hormonal Factorsmentioning

confidence: 99%

Mastitis in Autoimmune Diseases: Review of the Literature, Diagnostic Pathway, and Pathophysiological Key Players

Goulabchand

Hafidi

Perre

et al. 2020

JCM

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Mastitis frequently affects women of childbearing age. Of all the pathological breast conditions requiring specific management, autoimmune mastitis is in the third position after infection and breast cancer. The aim of this literature review was to make a comprehensive description of autoimmune diseases targeting the mammary gland. Four main histological patterns of autoimmune mastitis are described: (i) lymphocytic infiltrates; (ii) ductal ectasia; (iii) granulomatous mastitis; and (iv) vasculitis. Our literature search found that all types of autoimmune disease may target the mammary gland: organ-specific diseases (diabetes, thyroiditis); connective tissue diseases (such as systemic erythematosus lupus or Sjögren’s syndrome); vasculitides (granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, giant cell arteritis, polyarteritis nodosa, Behçet’s disease); granulomatous diseases (sarcoidosis, Crohn’s disease); and IgG4-related disease. Cases of breast-specific autoimmune diseases have also been reported, including idiopathic granulomatous mastitis. These breast-limited inflammatory diseases are sometimes the first symptom of a systemic autoimmune disease. Although autoimmune mastitis is rare, it is probably underdiagnosed or misdiagnosed. Early diagnosis may allow us to detect systemic diseases at an earlier stage, which could help to initiate a prompt, appropriate therapeutic strategy. In case of suspected autoimmune mastitis, we hereby propose a diagnostic pathway and discuss the potential pathophysiological pathways leading to autoimmune breast damage.

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Estrogen Receptor α Deficiency Modulates TLR Ligand–Mediated PDC-TREM Expression in Plasmacytoid Dendritic Cells in Lupus-Prone Mice

Cited by 12 publications

References 39 publications

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

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

Hormonal Modulation of Dendritic Cells Differentiation, Maturation and Function: Implications for the Initiation and Progress of Systemic Autoimmunity

Mastitis in Autoimmune Diseases: Review of the Literature, Diagnostic Pathway, and Pathophysiological Key Players

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