| 1. |
- Barrett, Aidan, et al.
(författare)
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Physiological estrogen levels are dispensable for the sex difference in immune responses during allergen-induced airway inflammation
- 2023
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985. ; 228:3
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Tidskriftsartikel (refereegranskat)abstract
- Women show an increased prevalence of adult-onset asthma compared to men and previous studies have shown that testosterone inhibits while estrogen worsens allergen-induced airway inflammation. However, detailed knowledge about the aggravating effects of estrogen on immune responses remain unclear. Defining the effects of physiological levels of estrogen on immune responses in asthma would aid in the development of improved treatment strategies.In this study, the importance of estrogen for the sex difference in asthma was determined using a murine model of house dust mite (HDM)-induced airway inflammation on intact female and male mice, as well as on ovariectomized (OVX) female mice treated with a physiological dose of 17 beta-estradiol (E2). Innate and adaptive immune responses were defined in bronchoalveolar lavage fluid, mediastinal lymph node (mLN) and lung tissue.The results reveal increased numbers of lung eosinophils, macrophages, and dendritic cells in female but not in male mice after HDM challenge. Females also exhibit higher numbers of Th17 cells in both mLN and lung in response to HDM. However, treatment of OVX mice with physiological levels of E2 does not influence any of the analyzed cell populations.Together, this study confirms the previously reported sex difference in allergen-induced airway inflammation and show that female mice mount stronger innate and adaptive immune responses to HDM challenge, but these effects are not mediated by physiological levels of E2.
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| 2. |
- Corciulo, Carmen, et al.
(författare)
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Physiological levels of estradiol limit murine osteoarthritis progression
- 2022
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Ingår i: The Journal of endocrinology. - 0022-0795 .- 1479-6805. ; 255:2, s. 39-51
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Tidskriftsartikel (refereegranskat)abstract
- Among patients with knee osteoarthritis (OA), postmenopausal women are over-represented. The purpose of this study was to determine whether deficiency of female sex steroids affects OA progression and to evaluate the protective effect of treatment with a physiological dose of 17β-estradiol (E2) on OA progression using a murine model. Ovariectomy (OVX) of female mice was used to mimic a postmenopausal state. OVX or sham-operated mice underwent surgery for destabilization of the medial meniscus (DMM) to induce OA. E2 was administered in a pulsed manner for 2 and 8 weeks. OVX of OA mice did not influence the cartilage phenotype or synovial thickness, while both cortical and trabecular subchondral bone mineral density (BMD) decreased after OVX compared with sham-operated mice at 8 weeks post-DMM surgery. Additionally, OVX mice displayed decreased motor activity, reduced threshold of pain sensitivity, and increased number of T cells in the inguinal lymph nodes compared to sham-operated mice 2 weeks after OA induction. Eight weeks of treatment with E2 prevented cartilage damage and thickening of the synovium in OVX OA mice. The motor activity was improved after E2 replacement at the 2 weeks time point, which was also associated with lower pain sensitivity in the OA paw. E2 treatment protected against OVX-induced loss of subchondral trabecular bone. The number of T cells in the inguinal lymph nodes was reduced by E2 treatment after 8 weeks. This study demonstrates that treatment with a physiological dose of E2 exerts a protective role by reducing OA symptoms.
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| 3. |
- Corciulo, Carmen, et al.
(författare)
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Physiological levels of estradiol limit murine osteoarthritis progression
- 2022
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Ingår i: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 255:2, s. 39-51
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Tidskriftsartikel (refereegranskat)abstract
- Among patients with knee osteoarthritis (OA), postmenopausal women are over-represented. The purpose of this study was to determine whether deficiency of female sex steroids affects OA progression and to evaluate the protective effect of treatment with a physiological dose of 17 beta-estradiol (E2) on OA progression using a murine model. Ovariectomy (OVX) of female mice was used to mimic a postmenopausal state. OVX or sham-operated mice underwent surgery for destabilization of the medial meniscus (DMM) to induce OA. E2 was administered in a pulsed manner for 2 and 8 weeks. OVX of OA mice did not influence the cartilage phenotype or synovial thickness, while both cortical and trabecular subchondral bone mineral density (BMD) decreased after OVX compared with sham-operated mice at 8 weeks post-DMM surgery. Additionally, OVX mice displayed decreased motor activity, reduced threshold of pain sensitivity, and increased number of T cells in the inguinal lymph nodes compared to sham-operated mice 2 weeks after OA induction. Eight weeks of treatment with E2 prevented cartilage damage and thickening of the synovium in OVX OA mice. The motor activity was improved after E2 replacement at the 2 weeks time point, which was also associated with lower pain sensitivity in the OA paw. E2 treatment protected against OVX-induced loss of subchondral trabecular bone. The number of T cells in the inguinal lymph nodes was reduced by E2 treatment after 8 weeks. This study demonstrates that treatment with a physiological dose of E2 exerts a protective role by reducing OA symptoms.
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| 4. |
- Corciulo, Carmen, et al.
(författare)
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Pulsed administration for physiological estrogen replacement in mice
- 2021
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Ingår i: F1000Research. - : F1000 Research Ltd. - 2046-1402 .- 1759-796X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens are important regulators of body physiology and have major effects on metabolism, bone, the immune- and central nervous systems. The specific mechanisms underlying the effects of estrogens on various cells, tissues and organs are unclear and mouse models constitute a powerful experimental tool to define the physiological and pathological properties of estrogens. Menopause can be mimicked in animal models by surgical removal of the ovaries and replacement therapy with 17β-estradiol in ovariectomized (OVX) mice is a common technique used to determine specific effects of the hormone. However, these studies are complicated by the non-monotonic dose-response of estradiol, when given as therapy. Increased knowledge of how to distribute estradiol in terms of solvent, dose, and administration frequency, is required in order to accurately mimic physiological conditions in studies where estradiol treatment is performed. In this study, mice were OVX and treated with physiological doses of 17β-estradiol-3-benzoate (E2) dissolved in miglyol or PBS. Subcutaneous injections were performed every 4 days to resemble the estrus cycle in mice. Results show that OVX induces an osteoporotic phenotype, fat accumulation and impairment of the locomotor ability, as expected. Pulsed administration of physiological doses of E2 dissolved in miglyol rescues the phenotypes induced by OVX. However, when E2 is dissolved in PBS the effects are less pronounced, possibly due to rapid wash out of the steroid.
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| 5. |
- Dubiela, P., et al.
(författare)
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Two patients with allergy to celery - Possible role of carbohydrate determinants and difference between seeds and tuber allergenicity
- 2022
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Ingår i: World Allergy Organization Journal. - : Elsevier BV. - 1939-4551. ; 15:11
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Tidskriftsartikel (refereegranskat)abstract
- Vegetables provide important nutrients but can also induce allergic symptoms. Celery tuber al-lergy frequently occurs in Central European countries and can cause allergic reactions including fatal anaphylactic shocks. There is little information about allergen content in seeds. Therefore, we analyzed 2 patients with allergic reaction after remoulade sauce consumption who entered the clinic for a diagnostic work-up. The routine diagnostic included serum derived specific IgE testing by ImmunoCAP, ImmunoCAP ISAC, and skin prick tests (SPTs). Furthermore, protein extracts were prepared from both celery tuber and celery seeds and IgE binding capacity of these extracts was assessed by immunoblots, ELISA, and rat basophil leukemia (RBL) assay. We also determined role of cross-reactive carbohydrate determinants (CCDs) by IgE inhibition ELISA. Results revealed distinct protein patterns from celery tuber and seed extracts, suggesting differences in content and quantity of allergenic proteins. IgE antibodies from both sera bound to high molecular weight (HMW) proteins on immunoblots and caused high basophil response, which was also observed upon addition of glycosylated proteins as horseradish peroxidase and Api g 5, respectively. Our results indicate that it is worth considering CCDs from plant foods as a possible allergenic factor and their contribution to the mugwort-celery syndrome.
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| 6. |
- Humeniuk, Piotr, et al.
(författare)
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Profiling of innate and adaptive immune cells during influenza virus infection reveals sex bias in invariant natural killer T (iNKT) cells
- 2023
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Ingår i: Immunity, Inflammation and Disease. - 2050-4527. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Influenza A virus (IAV) infection leads to significant morbidity and mortality. Biological sex influences the immune responses to IAV infection, resulting in higher mortality in women of reproductive age. Previous studies revealed increased activation of T and B cells in female mice after IAV infection, but extensive analysis of sex differences in both innate and adaptive immune cells over time is lacking. Invariant natural killer T (iNKT) cells are fast-reacting forces and modulators of immune responses that are important to IAV immunity, but it is not known if the presence and function of iNKT cells differ between females and males. The aim of this study was to determine immunological mechanisms that contribute to the increased disease severity in female mice during IAV infection. Methods: Female and male mice were infected with mouse-adapted IAV and monitored for weight loss and survival. Immune cell populations and cytokine expression in bronchoalveolar lavage fluid, lung, and mediastinal lymph node were determined at three time points after infection using flow cytometry and ELISA. Results: The results reveal increased severity and mortality in adult female mice compared to age- matched males. Female mice show larger increases in innate and adaptive immune cell populations and cytokine production in lung compared to mock on Day 6 postinfection. On Day 9 postinfection, female mice express higher numbers of iNKT cells in lung and liver compared to males. Conclusions: This comprehensive analysis of immune cells and cytokines over time following IAV infection reveals increased leukocyte expansion and stronger proinflammatory cytokine responses in female mice during disease initiation. Furthermore, this is the first study to report a sex bias in iNKT cell populations after IAV infection. The data suggests that the process of recovery from IAV-induced airway inflammation is associated with increased expansion of several different iNKT cell subpopulations in female mice.
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| 7. |
- Scheffler, Julia M., et al.
(författare)
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ER alpha Signaling in a Subset of CXCL12-Abundant Reticular Cells Regulates Trabecular Bone in Mice
- 2022
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Ingår i: JBMR Plus. - : Wiley. - 2473-4039. ; 6:8
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen has pronounced effects on the immune system, which also influences bone homeostasis. In recent years, stromal cells in lymphoid organs have gained increasing attention as they not only support the regulation of immune responses but also affect bone remodeling. A conditional knockout mouse model where estrogen receptor alpha (ER alpha) is deleted in CCL19-expressing stromal cells (Ccl19-Cre ER alpha(fl/fl) mice) was generated and bone densitometry was performed to analyze the importance of stromal cell-specific ER alpha signaling on the skeleton. Results showed that female Ccl19-Cre ER alpha(fl/fl) mice display reduced total bone mineral density and detailed X-ray analyses revealed that ER alpha expression in CCL19-expressing stromal cells is important for trabecular but not cortical bone homeostasis. Further analysis showed that the trabecular bone loss is caused by increased osteoclastogenesis. Additionally, the bone formation rate was reduced; however, the expression of osteoprogenitor genes was not altered. Analysis of the bone marrow stromal cell compartment revealed a deletion of ER alpha in a subgroup of CXCL12-abundant reticular (CAR) cells resulting in increased secretion of the pro-osteoclastogenic chemokine CXCL12. In conclusion, this study reveals the importance of ER alpha signaling in CAR cells for bone health. (c) 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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