Breast-feeding regulates immune system development via transforming growth factor-β in mice pups

2018 ◽  
Vol 60 (3) ◽  
pp. 224-231 ◽  
Author(s):  
Keita Sakaguchi ◽  
Akemi Koyanagi ◽  
Fumitaka Kamachi ◽  
Akiko Harauma ◽  
Asako Chiba ◽  
...  
Keyword(s):  
Immune System ◽  
Growth Factor ◽  
Breast Feeding ◽  
Transforming Growth Factor ◽  
System Development ◽  
Transforming Growth Factor Β ◽  
Immune System Development

scholarly journals Targeting Transforming Growth Factor β to Enhance Cancer Immunotherapy

2006 ◽  
Vol 13 (4) ◽  
pp. 141-143 ◽  
Author(s):  
T. Hahn ◽  
Emmanuel Akporiaye
Keyword(s):  
Immune System ◽  
Growth Factor ◽  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Human Tumours

Human tumours have evolved intricate mechanisms to evade the immune system, either by avoiding recognition or by inhibiting and eliminating immune cells. [...]

scholarly journals Transforming Growth Factor β Subverts the Immune System into Directly Promoting Tumor Growth through Interleukin-17

2008 ◽  
Vol 68 (10) ◽  
pp. 3915-3923 ◽  
Author(s):  
Jeong-Seok Nam ◽  
Masaki Terabe ◽  
Mi-Jin Kang ◽  
Helen Chae ◽  
Nga Voong ◽  
...  
Keyword(s):  
Immune System ◽  
Growth Factor ◽  
Tumor Growth ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 17

A GMCSF & IL15 Fusokine Leads to Paradoxical Immunosuppression In Vivo Via Asymmetrical JAK/STAT Signalling through the IL15 Receptor Complex.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3187-3187
Author(s):  
Moutih Rafei ◽  
Jian Hui Wu ◽  
Borhane Annabi ◽  
Laurence Lejeune ◽  
Moira Francois ◽  
...  
Keyword(s):  
Immune System ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
De Novo ◽  
Adaptive Immune System ◽  
Transforming Growth Factor Β ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Mouse Splenocytes

Abstract Immune stimulatory cytokines can be exploited to treat human ailments including cancer. Amongst cytokines identified for such use, granulocyte-macrophage colony stimulating factor (GMCSF) has been under much scrutiny since it acts directly on the adaptive immune system by enhancing antigen presentation as well as costimulation. Furthermore, interleukin (IL)15 possesses overlapping activities with IL2 such as the activation of T-cells and the stimulation of natural killing as well as additive stimulatory effects on the immune system distinct from IL2. These features make IL15 an attractive companion to GMCSF as part of an immunotherapeutic fusokine. Therefore, we hypothesized that a GMCSF and IL15 fusion protein (GIFT15) would possess greater immune stimulatory properties than their combined use. Unexpectedly, tumor cells engineered to secrete GIFT15 protein led to enhanced tumor growth and suppression of natural killer (NK) and NKT-cell recruitment in vivo, suggesting an unheralded immune suppressive effect. We found that GIFT15 has pleiotropic effects on an array of immune competent cells. More specifically, peritoneal macrophages treatment with GIFT15 secrete de novo the tissue inhibitor of metalloproteinase-2 (TIMP-2); activated matrix metalloproteinase-2 (MMP-2); transforming growth factor-β (TGF-β) as well as vascular endothelial growth factor (VEGF). In terms of ligand-receptor interactions, we show by BIAcore analysis that the GIFT15 fusokine has increased affinity for the αchain component of the trimeric IL15R, which contributes to aberrant signalling through the β chain manifested by the hyperphosphorylation of STAT3 both in macrophages and splenocytes. In addition, GIFT15 and IL15R virtual interaction studies suggests that the GMCSF domain component of the GIFT15 fusokine may hinder the interaction of the IL15 domain component with the IL15Rγ chain, and thus leading to a downregulation of the JAK3/STAT5 pathway. We also show that GIFT15 leads to suppression of common γ chain-mediated STAT5 phosphorylation and blockade of the IL15-dependent IFN-γ response in mouse splenocytes We tested the utlity of GIFT15 as an immunosuppressor directly in vivo and demonstrated that it allowed engraftment of allogeneic B16F0 and human xenograft U87MG glioma cells in immunocompetent mice in a CD4-dependent maner. Thus, GIFT15 defines a new class of fusokine which mediates pro-angiogenic and potent immunosuppressive effects via aberrant signalling by the IL15R in lymphomyeloid cells. We propose that GIFT15 may serve as a novel pharmaceutical for tolerance induction of somatic allo or xenografts in mammals without requirement of toxic conditioning regimens.

scholarly journals Targeted Disruption of Smad3 Reveals an Essential Role in Transforming Growth Factor β-Mediated Signal Transduction

1999 ◽  
Vol 19 (4) ◽  
pp. 2495-2504 ◽  
Author(s):  
Michael B. Datto ◽  
Joshua P. Frederick ◽  
Lihua Pan ◽  
Anita J. Borton ◽  
Yuan Zhuang ◽  
...  
Keyword(s):  
Immune System ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Dermal Fibroblasts ◽  
Null Mouse ◽  
Developmental Defect ◽  
Plasminogen Activator Inhibitor 1 ◽  
Targeted Disruption

ABSTRACT The Smads are a family of nine related proteins which function as signaling intermediates for the transforming growth factor β (TGF-β) superfamily of ligands. To discern the in vivo functions of one of these Smads, Smad3, we generated mice harboring a targeted disruption of this gene. Smad3 null mice, although smaller than wild-type littermates, are viable, survive to adulthood, and exhibit an early phenotype of forelimb malformation. To study the cellular functions of Smad3, we generated Smad3 null mouse embryonic fibroblasts (MEFs) and dermal fibroblasts. We demonstrate that null MEFs have lost the ability to form Smad-containing DNA binding complexes and are unable to induce transcription from the TGF-β-responsive promoter construct, p3TP-lux. Using the primary dermal fibroblasts, we also demonstrate that Smad3 is integral for induction of endogenous plasminogen activator inhibitor 1. We subsequently demonstrate that Smad3 null MEFs are partially resistant to TGF-β’s antiproliferative effect, thus firmly establishing a role for Smad3 in TGF-β-mediated growth inhibition. We next examined cells in which Smad3 is most highly expressed, specifically cells of immune origin. Although no specific developmental defect was detected in the immune system of the Smad3 null mice, a functional defect was observed in the ability of TGF-β to inhibit the proliferation of splenocytes activated by specific stimuli. In addition, primary splenocytes display defects in TGF-β-mediated repression of cytokine production. These data, taken together, establish a role for Smad3 in mediating the antiproliferative effects of TGF-β and implicate Smad3 as a potential effector for TGF-β in modulating immune system function.

scholarly journals A máj és az immunrendszer

2015 ◽  
Vol 156 (30) ◽  
pp. 1203-1213 ◽  
Author(s):  
Lajos Jakab
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Growth Factor ◽  
B Lymphocytes ◽  
Acute Phase ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Acute Phase Reaction ◽  
Specific Immune Response ◽  
Phase Reaction

The liver is known to be the metabolic centre of the organism and is under the control of the central nervous system. It has a peculiar tissue structure and its anatomic localisation defines it as part of the immune system having an individual role in the defence of the organism. The determinant of its particular tissue build-up is the sinusoid system. In addition to hepatocytes, one cell row “endothelium”, stellate cells close to the external surface, Kupffer cells tightly to its inner surface, as well as dendritic cells and other cell types (T and B lymphocytes, natural killer and natural killer T-cells, mast cells, granulocytes) are present. The multitudes and variety of cells make it possible to carry out the tasks according to the assignment of the organism. The liver is a member of the immune system having immune cells largely in an activated state. Its principal tasks are the assurance of the peripheral immune tolerance of the organism with the help of the haemopoetic cells and transforming growth factor-β. The liver takes part in the determination of the manner of the non-specific immune response of the organism. In addition to acute phase reaction of the organism, the liver has a role in the adaptive/specific immune response. These functions include retardation of the T and B lymphocytes and the defence against harmful pathogens. With the collaboration of transforming growth factor-β, immunoglobulins and their subclasses are inhibited just as the response of the T lymphocytes. The only exception is the undisturbed immunoglobulin A production. Particularly important is the intensive participation of the liver in the acute phase reaction of the organism, which is organised and guided by the coordinated functions of the cortico-hypothalamo-hypophysis-adrenal axis. Beside cellular elements, hormones, adhesion molecules, chemokines and cytokines are also involved in the cooperation with the organs. Acute phase reactants play a central role in these processes. Until recently the α2-macroglobulin was not considered as an acute reactant of the organism, but it is now functionally included in the acute phase reaction presumably due to its close connection with the transforming growth factor-β. Transforming growth factor-β has extraordinarily important roles in all phases of inflammation and in the specific immune response. The peripheral immune tolerance of the organism involves tightly coupled regulation of proliferation, differentiation and survival of lymphocytes. Orv. Hetil., 2015, 156(30), 1203–1213.

Perianale Fisteln bei CED: vom Mausmodell zur Klinik

2018 ◽  
Vol 75 (5) ◽  
pp. 287-294
Author(s):  
Michael Scharl
Keyword(s):  
Growth Factor ◽  
Morbus Crohn ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 13

Zusammenfassung. Fisteln stellen nach wie vor eine der wichtigsten Komplikationen bei Patienten mit Morbus Crohn dar. Bei mindestens einem Drittel aller Morbus Crohn Patienten treten im Laufe der Erkrankung Fisteln auf. Eine dauerhafte Heilung der Fistel wird jedoch, auch unter Ausschöpfung sämtlicher medikamentöser und chirurgischer Therapieoptionen, nur in rund einem Drittel dieser Patienten erreicht. Der genaue molekulare Mechanismus der Fistelentstehung ist bis heute nicht ganz klar. Aus histopathologischer Sichtweise stellen Fisteln eine röhrenartige Struktur dar, welche von flachen epithelartigen Zellen ausgekleidet ist. Als ursächlicher Entstehungsmechanismus wird dabei die sogenannte epitheliale-zu-mesenchymale Transition (EMT) angesehen und es kann eine starke Expression der Entzündungsmediatoren Tumor Nekrose Faktor, Interleukin-13 und Transforming Growth Factor β in den Fistelarealen nachgewiesen werden. Zusätzlich zu den bereits etablierten, medikamentösen Therapieoptionen, also Antibiotika, Immunmodulatoren und anti-TNF Antikörper, stellt insbesondere der Einsatz der mesenchymalen Stammzelltherapie einen erfolgversprechenden Therapieansatz für die Zukunft dar.

Sign in / Sign up

Export Citation Format

Share Document