scholarly journals IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC–activated Th2 memory cells

2007 ◽  
Vol 204 (8) ◽  
pp. 1837-1847 ◽  
Author(s):  
Yui-Hsi Wang ◽  
Pornpimon Angkasekwinai ◽  
Ning Lu ◽  
Kui Shin Voo ◽  
Kazuhiko Arima ◽  
...  
Keyword(s):  
Allergic Inflammation ◽  
Cell Types ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Target Cells ◽  
Memory Cells ◽  
Independent Manner ◽  
Distinct Member ◽  
Innate Effector

Interleukin (IL) 25 (IL-17E), a distinct member of the IL-17 cytokine family, plays important roles in evoking T helper type 2 (Th2) cell–mediated inflammation that features the infiltrations of eosinophils and Th2 memory cells. However, the cellular sources, target cells, and underlying mechanisms remain elusive in humans. We demonstrate that human Th2 memory cells expressing distinctive levels of IL-25 receptor (R) are one of the responding cell types. IL-25 promotes cell expansion and Th2 cytokine production when Th2 central memory cells are stimulated with thymic stromal lymphopoietin (TSLP)–activated dendritic cells (DCs), homeostatic cytokines, or T cell receptor for antigen triggering. The enhanced functions of Th2 memory cells induced by IL-25 are associated with sustained expression of GATA-3, c-MAF, and JunB in an IL-4–independent manner. Although keratinocytes, mast cells, eosinophils, and basophils express IL-25 transcripts, activated eosinophils and basophils from normal and atopic subjects were found to secrete bioactive IL-25 protein, which augments the functions of Th2 memory cells. Elevated expression of IL-25 and IL-25R transcripts was observed in asthmatic lung tissues and atopic dermatitis skin lesions, linking their possible roles with exacerbated allergic disorders. Our results provide a plausible explanation that IL-25 produced by innate effector eosinophils and basophils may augment the allergic inflammation by enhancing the maintenance and functions of adaptive Th2 memory cells.

scholarly journals Selective deletion of SHIP-1 in hematopoietic cells in mice leads to severe lung inflammation involving ILC2 cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xujun Ye ◽  
Fengrui Zhang ◽  
Li Zhou ◽  
Yadong Wei ◽  
Li Zhang ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Airway Remodeling ◽  
Pulmonary Inflammation ◽  
Hematopoietic Cells ◽  
Cell Lineage ◽  
Allergic Inflammation ◽  
Cell Types ◽  
Lymphoid Cells ◽  
Whole Body

AbstractSrc homology 2 domain–containing inositol 5-phosphatase 1 (SHIP-1) regulates the intracellular levels of phosphotidylinositol-3, 4, 5-trisphosphate, a phosphoinositide 3–kinase (PI3K) product. Emerging evidence suggests that the PI3K pathway is involved in allergic inflammation in the lung. Germline or induced whole-body deletion of SHIP-1 in mice led to spontaneous type 2-dominated pulmonary inflammation, demonstrating that SHIP-1 is essential for lung homeostasis. However, the mechanisms by which SHIP-1 regulates lung inflammation and the responsible cell types are still unclear. Deletion of SHIP-1 selectively in B cells, T cells, dendritic cells (DC) or macrophages did not lead to spontaneous allergic inflammation in mice, suggesting that innate immune cells, particularly group 2 innate lymphoid cells (ILC2 cells) may play an important role in this process. We tested this idea using mice with deletion of SHIP-1 in the hematopoietic cell lineage and examined the changes in ILC2 cells. Conditional deletion of SHIP-1 in hematopoietic cells in Tek-Cre/SHIP-1 mice resulted in spontaneous pulmonary inflammation with features of type 2 immune responses and airway remodeling like those seen in mice with global deletion of SHIP-1. Furthermore, when compared to wild-type control mice, Tek-Cre/SHIP-1 mice displayed a significant increase in the number of IL-5/IL-13 producing ILC2 cells in the lung at baseline and after stimulation by allergen Papain. These findings provide some hints that PI3K signaling may play a role in ILC2 cell development at baseline and in response to allergen stimulation. SHIP-1 is required for maintaining lung homeostasis potentially by restraining ILC2 cells and type 2 inflammation.

scholarly journals Human Dendritic Cells Mediate Cellular Apoptosis via Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (Trail)

1999 ◽  
Vol 190 (8) ◽  
pp. 1155-1164 ◽  
Author(s):  
Neil A. Fanger ◽  
Charles R. Maliszewski ◽  
Ken Schooley ◽  
Thomas S. Griffith
Keyword(s):  
Dendritic Cells ◽  
Tumor Cells ◽  
Cell Types ◽  
Target Cells ◽  
Functional Difference ◽  
Cellular Apoptosis ◽  
Soluble Trail ◽  
Innate Effector ◽  
Human Dendritic Cells ◽  
Necrosis Factor

TRAIL (TNF-related apoptosis-inducing ligand) is a member of the TNF family that induces apoptosis in a variety of cancer cells. In this study, we demonstrate that human CD11c+ blood dendritic cells (DCs) express TRAIL after stimulation with either interferon (IFN)-γ or -α and acquire the ability to kill TRAIL-sensitive tumor cell targets but not TRAIL-resistant tumor cells or normal cell types. The DC-mediated apoptosis was TRAIL specific, as soluble TRAIL receptor blocked target cell death. Moreover, IFN-stimulated interleukin (IL)-3 receptor (R)α+ blood precursor (pre-)DCs displayed minimal cytotoxicity toward the same target cells, demonstrating a clear functional difference between the CD11c+ DC and IL-3Rα+ pre-DC subsets. These results indicate that TRAIL may serve as an innate effector molecule on CD11c+ DCs for the elimination of spontaneously arising tumor cells and suggest a means by which TRAIL-expressing DCs may regulate or eliminate T cells responding to antigen presented by the DCs.

scholarly journals IL-33, an Alarmin of the IL-1 Family Involved in Allergic and Non Allergic Inflammation: Focus on the Mechanisms of Regulation of Its Activity

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 107
Author(s):  
Corinne Cayrol
Keyword(s):  
Interleukin 1 ◽  
Allergic Inflammation ◽  
Proteolytic Processing ◽  
Lymphoid Cells ◽  
Target Cells ◽  
Interleukin 33 ◽  
Promising Therapeutic Target ◽  
St2 Receptor ◽  
Barrier Tissues

Interleukin-33 (IL-33) is a member of the interleukin-1 (IL-1) family that is expressed in the nuclei of endothelial and epithelial cells of barrier tissues, among others. It functions as an alarm signal that is released upon tissue or cellular injury. IL-33 plays a central role in the initiation and amplification of type 2 innate immune responses and allergic inflammation by activating various target cells expressing its ST2 receptor, including mast cells and type 2 innate lymphoid cells. Depending on the tissue environment, IL-33 plays a wide variety of roles in parasitic and viral host defense, tissue repair and homeostasis. IL-33 has evolved a variety of sophisticated regulatory mechanisms to control its activity, including nuclear sequestration and proteolytic processing. It is involved in many diseases, including allergic, inflammatory and infectious diseases, and is a promising therapeutic target for the treatment of severe asthma. In this review, I will summarize the literature around this fascinating pleiotropic cytokine. In the first part, I will describe the basics of IL-33, from the discovery of interleukin-33 to its function, including its expression, release and signaling pathway. The second part will be devoted to the regulation of IL-33 protein leading to its activation or inactivation.

scholarly journals Human 17 β-hydroxysteroid dehydrogenase type 1 and type 2 isoenzymes have opposite activities in cultured cells and characteristic cell- and tissue-specific expression

1996 ◽  
Vol 314 (3) ◽  
pp. 839-845 ◽  
Author(s):  
Minna M. MIETTINEN ◽  
Mika V. J. MUSTONEN ◽  
Matti H. POUTANEN ◽  
Veli V. ISOMAA ◽  
Reijo K. VIHKO
Keyword(s):  
Cultured Cells ◽  
Cell Types ◽  
Hydroxysteroid Dehydrogenase ◽  
Enzyme Concentration ◽  
Sex Steroid ◽  
Target Cells ◽  
Specific Expression ◽  
Peripheral Tissues

17β-Hydroxysteroid dehydrogenase (17HSD) isoenzymes catalyse the interconversion between highly active 17β-hydroxy-and low-activity 17-keto-steroids and thereby regulate the biological activity of sex steroids. The present study was carried out to characterize 17HSD activity and the expression of 17HSD type 1 and 2 isoenzymes in several human cell types and tissues. The data indicate that in cultured cells the direction of 17HSD activity is exclusively determined by the expression of these distinct isoenzymes. The intracellular environment could not modulate the direction of the enzyme activities in any of the cell types analysed. 17HSD type 1 acts as a reductase converting oestrone into oestradiol, whereas 17HSD type 2 possesses oxidative activity inactivating oestradiol by converting it into oestrone. The data, furthermore, suggest that of the two 17HSD type 1 mRNAs (1.3 and 2.3 kb), expression of the 1.3 kb mRNA is related to enzyme concentration in all the cell types studied. This mRNA is principally expressed in cells of placental and ovarian origin, but is also present in malignant breast epithelial cells. In contrast, 17HSD type 2 is more widely expressed. It is present in several oestradiol-metabolizing tissues as well as in some target cells of sex steroid action. The opposite reaction directions observed in the cultured cells, together with differences in the distribution of the isoenzymes, suggest that type 1 is involved in oestradiol production in females while type 2 plays a role in the inactivation of this sex steroid in peripheral tissues, both in females and in males. However, some examples exist of simultaneous expression of both enzymes in the same cell type or tissue.

scholarly journals Cysteinyl leukotrienes mediate lymphokine killer activity induced by NKG2D and IL-15 in cytotoxic T cells during celiac disease

2015 ◽  
Vol 212 (10) ◽  
pp. 1487-1495 ◽  
Author(s):  
Fangming Tang ◽  
Benjamin Sally ◽  
Kathryn Lesko ◽  
Valentina Discepolo ◽  
Valerie Abadie ◽  
...  
Keyword(s):  
T Cells ◽  
Celiac Disease ◽  
Cytotoxic T Cells ◽  
Cell Receptor ◽  
Target Cells ◽  
T Helper 1 ◽  
Independent Manner ◽  
Killer Activity ◽  
Cysteinyl Leukotrienes ◽  
Organ Specific

Eicosanoids are inflammatory mediators that play a key but incompletely understood role in linking the innate and adaptive immune systems. Here, we show that cytotoxic effector T cells (CTLs) are capable of both producing and responding to cysteinyl leukotrienes (CystLTs), allowing for the killing of target cells in a T cell receptor–independent manner. This process is dependent on the natural killer receptor NKG2D and exposure to IL-15, a cytokine induced in distressed tissues. IL-15 and NKG2D signaling drives the up-regulation of key enzymes implicated in the synthesis of CystLTs, as well as the expression of CystLT receptors, suggesting a positive feedback loop. Finally, although the CystLT pathway has been previously linked to various allergic disorders, we provide unexpected evidence for its involvement in the pathogenesis of celiac disease (CD), a T helper 1 cell–mediated enteropathy induced by gluten. These findings provide new insights into the cytolytic signaling pathway of NKG2D and the pathogenesis of organ-specific immune disorders. Furthermore, they suggest that the blockade of CystLT receptors may represent a potent therapeutic target for CD or potentially other autoimmune disorders in which NKG2D has been implicated.

scholarly journals Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s

2016 ◽  
Vol 214 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Jakob von Moltke ◽  
Claire E. O’Leary ◽  
Nora A. Barrett ◽  
Yoshihide Kanaoka ◽  
K. Frank Austen ◽  
...  
Keyword(s):  
T Cells ◽  
Allergic Inflammation ◽  
Primary Source ◽  
Cell Receptor ◽  
Lymphoid Cells ◽  
Th2 Cells ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Deficient Mice

Group 2 innate lymphoid cells (ILC2s) and type 2 helper T cells (Th2 cells) are the primary source of interleukin 5 (IL-5) and IL-13 during type 2 (allergic) inflammation in the lung. In Th2 cells, T cell receptor (TCR) signaling activates the transcription factors nuclear factor of activated T cells (NFAT), nuclear factor κB (NF-κB), and activator protein 1 (AP-1) to induce type 2 cytokines. ILC2s lack a TCR and respond instead to locally produced cytokines such as IL-33. Although IL-33 induces AP-1 and NF-κB, NFAT signaling has not been described in ILC2s. In this study, we report a nonredundant NFAT-dependent role for lipid-derived leukotrienes (LTs) in the activation of lung ILC2s. Using cytokine reporter and LT-deficient mice, we find that complete disruption of LT signaling markedly diminishes ILC2 activation and downstream responses during type 2 inflammation. Type 2 responses are equivalently attenuated in IL-33– and LT-deficient mice, and optimal ILC2 activation reflects potent synergy between these pathways. These findings expand our understanding of ILC2 regulation and may have important implications for the treatment of airways disease.

scholarly journals Digestive system is a potential route of COVID-19: an analysis of single-cell coexpression pattern of key proteins in viral entry process

Gut ◽  
2020 ◽  
Vol 69 (6) ◽  
pp. 1010-1018 ◽  
Author(s):  
Hao Zhang ◽  
Zijian Kang ◽  
Haiyi Gong ◽  
Da Xu ◽  
Jing Wang ◽  
...  
Keyword(s):  
Single Cell ◽  
Viral Entry ◽  
Digestive System ◽  
Cell Types ◽  
Cell Receptor ◽  
Host Cells ◽  
Target Cells ◽  
Sequencing Data ◽  
Transmembrane Serine Protease ◽  
Coexpression Pattern

ObjectiveSince December 2019, a newly identified coronavirus (severe acute respiratory syndrome coronavirus (SARS-CoV-2)) has caused outbreaks of pneumonia in Wuhan, China. SARS-CoV-2 enters host cells via cell receptor ACE II (ACE2) and the transmembrane serine protease 2 (TMPRSS2). In order to identify possible prime target cells of SARS-CoV-2 by comprehensive dissection of ACE2 and TMPRSS2 coexpression pattern in different cell types, five datasets with single-cell transcriptomes of lung, oesophagus, gastric mucosa, ileum and colon were analysed.DesignFive datasets were searched, separately integrated and analysed. Violin plot was used to show the distribution of differentially expressed genes for different clusters. The ACE2-expressing and TMPRRSS2-expressing cells were highlighted and dissected to characterise the composition and proportion.ResultsCell types in each dataset were identified by known markers. ACE2 and TMPRSS2 were not only coexpressed in lung AT2 cells and oesophageal upper epithelial and gland cells but also highly expressed in absorptive enterocytes from the ileum and colon. Additionally, among all the coexpressing cells in the normal digestive system and lung, the expression of ACE2 was relatively highly expressed in the ileum and colon.ConclusionThis study provides the evidence of the potential route of SARS-CoV-2 in the digestive system along with the respiratory tract based on single-cell transcriptomic analysis. This finding may have a significant impact on health policy setting regarding the prevention of SARS-CoV-2 infection. Our study also demonstrates a novel method to identify the prime cell types of a virus by the coexpression pattern analysis of single-cell sequencing data.

FcγRIII discriminates between 2 subsets of Vγ9Vδ2 effector cells with different responses and activation pathways

Blood ◽  
2004 ◽  
Vol 104 (6) ◽  
pp. 1801-1807 ◽  
Author(s):  
Daniela F. Angelini ◽  
Giovanna Borsellino ◽  
Mary Poupot ◽  
Adamo Diamantini ◽  
Rémy Poupot ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Cell Receptor ◽  
Interferon Γ ◽  
Effector Memory ◽  
Target Cells ◽  
Memory Cells ◽  
Effector Cells ◽  
Lineage Differentiation ◽  
Ifn Γ ◽  
Low Levels

Abstract Upon recognition of nonpeptidic phosphoantigens, human Vδ2 T lymphocytes enter a lineage differentiation pattern that determines the generation of memory cells with a range of effector functions. Here, we show that within the effector memory Vδ2 population, 2 distinct and complementary subsets with regard to phenotype, mode of activation, and type of responses can be identified: Vδ2 TEMh cells, which express high levels of chemokine receptors, but low levels of perforin and of natural killer receptors (NKRs) and which produce large amounts of interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) in response to T-cell receptor (TCR)–specific stimulation by phosphoantigens; and Vδ2TEMRA cells, which constitutively express several NKRs, high amounts of perforin, but low levels of chemokine receptors and of IFN-γ. These NK-like cells are refractory to phosphoantigen but respond to activation via FcγRIII (CD16) and are highly active against tumoral target cells. Thus, circulating Vδ2T lymphocytes comprise 2 functionally diverse subsets of effector memory cells that may be discriminated on the basis of CD16 expression.

scholarly journals Cell-Type-Specific Characteristics Modulate the Transduction Efficiency of Adeno-Associated Virus Type 2 and Restrain Infection of Endothelial Cells

2002 ◽  
Vol 76 (22) ◽  
pp. 11530-11540 ◽  
Author(s):  
Katri Pajusola ◽  
Marcin Gruchala ◽  
Hana Joch ◽  
Thomas F. Lüscher ◽  
Seppo Ylä-Herttuala ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Types ◽  
Target Cells ◽  
Cell Type ◽  
Permissive Cell ◽  
Endosomal Acidification ◽  
Cell Type Specific ◽  
Different Cell Types

ABSTRACT Adeno-associated viruses (AAVs) are promising vectors for various gene therapy applications due to their long-lasting transgene expression and wide spectrum of target cells. Recently, however, it has become apparent that there are considerable differences in the efficiencies of transduction of different cell types by AAVs. Here, we analyzed the efficiencies of transduction and the transport mechanisms of AAV type 2 (AAV-2) in different cell types, emphasizing endothelial cells. Expression analyses in both cultured cells and the rabbit carotid artery assay showed a remarkably low level of endothelial cell transduction in comparison to the highly permissive cell types. The study of the endosomal pathways of AAV-2 with fluorescently labeled virus showed clear targeting of the Golgi area in permissive cell lines, but this phenomenon was absent in the endothelial cell line EAhy-926. On the other hand, the response to the block of endosomal acidification by bafilomycin A1 also showed differences among the permissive cell types. We also analyzed the effect of proteasome inhibitors on endothelial cells, but their impact on the primary cells and in vivo was not significant. On the contrary, analysis of the expression pattern of heparan sulfate proteoglycans (HSPGs), the primary receptors of AAV-2, revealed massive deposits of HSPG in the extracellular matrix of endothelial cells. The matrix-associated receptors may therefore compete for virus binding and reduce transduction in endothelial cells. Accordingly, in endothelial cells detached from their matrix, AAV-2 transduction was significantly increased. Altogether, these results point to a more complex cell-type-specific mode of transduction of AAV-2 than previously appreciated.

Sign in / Sign up

Export Citation Format

Share Document