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- Rådinger, Madeleine, 1967, et al.
(author)
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Regulatory role of CD8+ T lymphocytes in bone marrow eosinophilopoiesis
- 2006
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In: Respir Res. - : Springer Science and Business Media LLC. - 1465-993X. ; 7
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Journal article (peer-reviewed)abstract
- BACKGROUND: There is a growing body of evidence to suggest that CD8+ T lymphocytes contribute to local allergen-induced eosinophilic inflammation. Since bone marrow (BM) responses are intricately involved in the induction of airway eosinophilia, we hypothesized that CD8+ T lymphocytes, as well as CD4+ T lymphocytes, may be involved in this process. METHODS: Several approaches were utilized. Firstly, mice overexpressing interleukin-5 (IL-5) in CD3+ T lymphocytes (NJ.1638; CD3IL-5+ mice) were bred with gene knockout mice lacking either CD4+ T lymphocytes (CD4-/-) or CD8+ T lymphocytes (CD8-/-) to produce CD3IL-5+ knockout mice deficient in CD4+ T lymphocytes (CD3IL-5+/CD4-/-) and CD8+ T lymphocytes (CD3IL-5+/CD8-/-), respectively. Secondly, CD3+, CD4+ and CD8+ T lymphocytes from naive CD3IL-5+ and C57BL/6 mice were adoptively transferred to immunodeficient SCID-bg mice to determine their effect on BM eosinophilia. Thirdly, CD3IL-5+, CD3IL-5+/CD8-/- and CD3IL-5+/CD4-/- mice were sensitized and allergen challenged. Bone marrow and blood samples were collected in all experiments. RESULTS: The number of BM eosinophils was significantly reduced in CD3IL-5+/CD8-/- mice compared to CD3IL-5+ mice and CD3IL-5+/CD4-/- mice. Serum IL-5 was significantly higher in CD3IL-5+/CD4-/- mice compared to CD3IL-5+ mice but there was no difference in serum IL-5 between CD3IL-5+/CD4-/- and CD3IL-5+/CD8-/- mice. Adoptive transfer of CD8+, but not CD4+ T lymphocytes from naive CD3IL-5+ and C57BL/6 mice restored BM eosinophilia in immunodeficient SCID-bg mice. Additionally, allergen challenged CD3IL-5+/CD8-/- mice developed lower numbers of BM eosinophils compared to CD3IL-5+ mice and CD3IL-5+/CD4-/- mice. CONCLUSION: This study shows that CD8+ T lymphocytes are intricately involved in the regulation of BM eosinophilopoiesis, both in non-sensitized as well as sensitized and allergen challenged mice.
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| 2. |
- Sergejeva, Svetlana, 1972, et al.
(author)
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Impact of IL-17 on cells of the monocyte lineage in health and disease.
- 2009
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In: Endocrine, metabolic & immune disorders drug targets. - 1871-5303. ; 9:2, s. 178-86
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Journal article (peer-reviewed)abstract
- Discovered in 1993, IL-17 has been the focus of intensive research during the last decade, in particular because of its neutrophil-accumulating capacity in several mammalian organs. We now know that the IL-17 family includes as a minimum 6 members, of whom at least IL-17A and IL-17F can be produced by T cells. Thus, IL-17 is positioned at the interface of acquired and innate immunity and constitutes a link between T cell activity and the accumulation of neutrophils locally in organs. Interestingly, there is now accumulating evidence that IL-17 has effects on myeloid cells other than neutrophils as well, namely on cells of the monocyte lineage. This review article scrutinizes the evidence that IL-17 exerts a functional impact on the cytokine production and functional activity in cells of the monocyte lineage in health and disease. Notably, this evidence includes data suggesting that there are conditions in which cells of the monocyte lineage are likely to play a significant pathogenic role and where IL-17 is directly controlling the activity of these key effector cells.
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| 3. |
- Sergejeva, Svetlana, 1972, et al.
(author)
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Increased number of CD34+ cells in nasal mucosa of allergic rhinitis patients: inhibition by a local corticosteroid.
- 2005
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In: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 0954-7894. ; 35:1, s. 34-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Eosinophils develop from CD34+ haematopoietic progenitor cells. Allergen exposure in susceptible individuals is known to induce a local eosinophilic inflammation, but the effect on progenitor cells is much less understood. OBJECTIVE: We aimed to evaluate how allergen exposure affects the number of tissue CD34+ cells and CD34+ eosinophils in allergic rhinitis (AR) patients and whether any such effect is influenced by local corticosteroid treatment. Also, we evaluated changes in the number of CXC receptor 4-positive cells (CXCR4+), since the CXCR4 ligand (stromal cell-derived factor-1 (SDF-1)) is a potent chemoattractant for haematopoietic progenitors. METHODS: In a double-blind, randomized study, pollen-sensitized AR patients were treated with a nasal corticosteroid fluticasone propionate (FP, 200 microg/day) or placebo throughout the pollen season. Nasal biopsies were taken before and during the season. CD34 and CXCR4 were stained using immunohistochemistry. RESULTS: The pollen season significantly increased the number of CD34+ cells, CD34+/CXCR4+ cells and CD34+ eosinophils in placebo-treated patients, but not in FP-treated patients. The mean pollen season-induced increase in CD34+ cells, CD34+/CXCR4+ cells and CD34+ eosinophils in FP-treated patients was lower compared with placebo-treated patients. CONCLUSION: A pollen season increases the number of CD34+ cells in nasal tissue accompanied by an increase in the number of CD34+/CXCR4+ haematopoietic progenitors and also the number of CD34+ eosinophils in subjects with AR. Treatment with a local corticosteroid provides protection against this pollen-induced increase in tissue CD34+ cells and CD34+ eosinophils possibly via inhibition of allergen-induced CXCR4-mediated recruitment of CD34+ haematopoietic progenitors into airways and their further differentiation into eosinophils within the tissue.
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| 4. |
- Sergejeva, Svetlana, 1972, et al.
(author)
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Interleukin-17 as a recruitment and survival factor for airway macrophages in allergic airway inflammation
- 2005
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In: American journal of respiratory cell and molecular biology. - 1044-1549. ; 33:3, s. 248-53
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Journal article (peer-reviewed)abstract
- Recent data indicate that the proinflammatory cytokine, interleukin (IL)-17, stimulates certain effector functions of human macrophages. We evaluated whether IL-17 mediates allergen-induced accumulation of airway macrophages and, if so, whether such an effect relates to the control of macrophage recruitment and survival. BALB/c mice were sensitized and challenged with ovalbumin. Three hours before challenge an anti-mouse IL-17 mAb (a-IL-17) was administered. Sampling was conducted 24 h after the allergen challenge. In vitro chemotaxis assay for blood monocytes and culture of airway macrophages, immunocytochemistry for Fas-antigen, and matrix metalloproteinase-9 (MMP-9) were used to determine the effect of IL-17 on the recruitment, survival, and activity of airway macrophages. A-IL-17 reduced the number of airway neutrophils and macrophages after allergen challenge. In vitro, recombinant IL-17 induced migration of blood monocytes and prolonged survival of airway macrophages. A-IL-17 also increased the expression of Fas-antigen in airway macrophages in vivo. Finally, the expression of MMP-9 by airway neutrophils and macrophages in vivo was downregulated by a-IL-17. This study indicates that endogenous IL-17 mediates the accumulation of macrophages during allergen-induced airway inflammation. IL-17 exerts its effects by acting directly on airway macrophages by promoting their recruitment and survival. Furthermore, IL-17 is involved in controlling the proteolytic activity of macrophages and neutrophils in allergen-induced airway inflammation.
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