scholarly journals The Role of IL-33/ST2 Pathway in Tumorigenesis

2018 ◽  
Vol 19 (9) ◽  
pp. 2676 ◽  
Author(s):  
Kristen Larsen ◽  
Maydelis Minaya ◽  
Vivek Vaish ◽  
Maria Peña
Keyword(s):  
Tumor Regression ◽  
Tumor Development ◽  
Tumor Stroma ◽  
Target Cells ◽  
Dual Function ◽  
T Helper ◽  
Interleukin 33 ◽  
T Helper 2 ◽  
Th2 Immune Response

Cancer is initiated by mutations in critical regulatory genes; however, its progression to malignancy is aided by non-neoplastic cells and molecules that create a permissive environment known as the tumor stroma or microenvironment (TME). Interleukin 33 (IL-33) is a dual function cytokine that also acts as a nuclear factor. IL-33 typically resides in the nucleus of the cells where it is expressed. However, upon tissue damage, necrosis, or injury, it is quickly released into extracellular space where it binds to its cognate receptor suppression of tumorigenicity 2 (ST2)L found on the membrane of target cells to potently activate a T Helper 2 (Th2) immune response, thus, it is classified as an alarmin. While its role in immunity and immune-related disorders has been extensively studied, its role in tumorigenesis is only beginning to be elucidated and has revealed opposing roles in tumor development. The IL-33/ST2 axis is emerging as a potent modulator of the TME. By recruiting a cohort of immune cells, it can remodel the TME to promote malignancy or impose tumor regression. Here, we review its multiple functions in various cancers to better understand its potential as a therapeutic target to block tumor progression or as adjuvant therapy to enhance the efficacy of anticancer immunotherapies.

scholarly journals Role of beta1 and beta2 subunits of the interleukin-12 receptor in determining T helper 1/T helper 2 responses in vivo in the rat

Immunology ◽  
2000 ◽  
Vol 99 (1) ◽  
pp. 109-112 ◽  
Author(s):  
K. M. Gillespie ◽  
C.-C. Szeto ◽  
V. M. Betin ◽  
P. W. Mathieson
Keyword(s):  
Interleukin 12 ◽  
T Helper ◽  
T Helper 1 ◽  
T Helper 2

scholarly journals Role of MSC in the Tumor Microenvironment

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2107 ◽  
Author(s):  
Ralf Hass
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Tumor Development ◽  
Tumor Stroma ◽  
Cell Types ◽  
Cellular Interactions ◽  
Cell Functions ◽  
Metastatic Behavior ◽  
Stem Cell Niches

The tumor microenvironment represents a dynamically composed matrix in which tissue-associated cancer cells are embedded together with a variety of further cell types to form a more or less separate organ-like structure. Constantly mutual interactions between cells of the tumor microenvironment promote continuous restructuring and growth in the tumor. A distinct organization of the tumor stroma also facilitates the formation of transient cancer stem cell niches, thereby contributing to progressive and dynamic tumor development. An important but heterogeneous mixture of cells that communicates among the cancer cells and the different tumor-associated cell types is represented by mesenchymal stroma-/stem-like cells (MSC). Following recruitment to tumor sites, MSC can change their functionalities, adapt to the tumor’s metabolism, undergo differentiation and synergize with cancer cells. Vice versa, cancer cells can alter therapeutic sensitivities and change metastatic behavior depending on the type and intensity of this MSC crosstalk. Thus, close cellular interactions between MSC and cancer cells can eventually promote cell fusion by forming new cancer hybrid cells. Consequently, newly acquired cancer cell functions or new hybrid cancer populations enlarge the plasticity of the tumor and counteract successful interventional strategies. The present review article highlights some important features of MSC within the tumor stroma.

Role of IL-4, IL-13, and STAT6 in inflammation-induced hypercontractility of murine smooth muscle cells

2002 ◽  
Vol 282 (2) ◽  
pp. G226-G232 ◽  
Author(s):  
Hirotada Akiho ◽  
Patricia Blennerhassett ◽  
Yikang Deng ◽  
Stephen M. Collins
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Trichinella Spiralis ◽  
Muscle Cells ◽  
Dependent Manner ◽  
T Helper ◽  
Concentration Dependent Manner ◽  
T Helper 2 ◽  
Muscularis Externa

T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13, which activate signal transducer and activator of transcription 6 (STAT6) are expressed in the muscularis externa during nematode infection and are candidate mediators of the associated hypercontractility. To determine the locus of action of these cytokines, we examined the IL-4- and IL-13-induced hypercontractility of the isolated muscle cells from STAT6 +/+ and STAT6 −/− mice. We compared the results with cells isolated from Trichinella spiralis-infected STAT6 +/+ and STAT6 −/− mice. Carbamylcholine chloride (Carbachol) induced the contraction of jejunal muscle cells in a concentration-dependent manner maximal contraction (Rmax26.7 ± 1.9%). Cells from T. spiralis-infected STAT6 −/− mice showed the hypertrophy (cell lengths 41.4 ± 0.8 to 89.0 ± 8.7 μm) and hypercontractility (Rmax37.5 ± 1.3%) induced by infection. IL-4Rα mRNA was detected in dispersed smooth muscle cells. Incubation of longitudinal muscle-myenteric plexus (LMMP) with IL-4 and IL-13 enhanced Carbachol-induced muscle contraction (Rmax35.5 ± 1.9 and 32.4 ± 2.9%, respectively). Incubation of LMMP from STAT6 −/− mice with IL-4 did not enhance the contraction. The hypercontractility in T. spiralis-infected mice was attenuated in STAT6 −/− mice ( P < 0.02). These results indicate both IL-4 and IL-13 induce hypercontractility of muscle cells via the STAT6 pathway, and this is the basis for hypercontractility observed in T. spiralis-infected mice.

scholarly journals Role of IL-33 and Its Receptor in T Cell-Mediated Autoimmune Diseases

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Qing Zhao ◽  
Guangjie Chen
Keyword(s):  
T Cell ◽  
Autoimmune Diseases ◽  
Host Defense ◽  
Interleukin 1 ◽  
Target Cells ◽  
Specific Receptor ◽  
Interleukin 33 ◽  
New Findings ◽  
Organ Specific

Interleukin-33 (IL-33) is a new cytokine of interleukin-1 family, whose specific receptor is ST2. IL-33 exerts its functions via its target cells and plays different roles in diseases. ST2 deletion and exclusion of IL-33/ST2 axis are accompanied by enhanced susceptibility to dominantly T cell-mediated organ-specific autoimmune diseases. It has been reported that IL-33/ST2 pathway plays a key role in host defense and immune regulation in inflammatory and infectious diseases. This review focuses on new findings in the roles of IL-33 and ST2 in several kinds of T cell-mediated autoimmune diseases.

scholarly journals The Interleukin-33-p38 Kinase Axis Confers Memory T Helper 2 Cell Pathogenicity in the Airway

Immunity ◽  
2015 ◽  
Vol 42 (2) ◽  
pp. 294-308 ◽  
Author(s):  
Yusuke Endo ◽  
Kiyoshi Hirahara ◽  
Tomohisa Iinuma ◽  
Kenta Shinoda ◽  
Damon J. Tumes ◽  
...  
Keyword(s):  
T Helper ◽  
P38 Kinase ◽  
Interleukin 33 ◽  
T Helper 2

scholarly journals The Th1:Th2 Dichotomy of Pregnancy and Preterm Labour

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Lynne Sykes ◽  
David A. MacIntyre ◽  
Xiao J. Yap ◽  
Tiong Ghee Teoh ◽  
Phillip R. Bennett
Keyword(s):  
Pregnancy Loss ◽  
Preterm Labour ◽  
Adverse Outcomes ◽  
T Helper ◽  
T Helper 1 ◽  
T Helper 2 ◽  
Infection And Inflammation ◽  
Therapeutic Measures ◽  
New Biomarkers

Pregnancy is a unique immunological state in which a balance of immune tolerance and suppression is needed to protect the fetus without compromising the mother. It has long been established that a bias from the T helper 1 cytokine profile towards the T helper 2 profile contributes towards successful pregnancy maintenance. The majority of publications that report on aberrant Th1:Th2 balance focus on early pregnancy loss and preeclampsia. Over the last few decades, there has been an increased awareness of the role of infection and inflammation in preterm labour, and the search for new biomarkers to predict preterm labour continues. In this paper, we explore the evidence for an aberrant Th1:Th2 profile associated with preterm labour. We also consider the potential for its use in screening women at high risk of preterm labour and for prophylactic therapeutic measures for the prevention of preterm labour and associated neonatal adverse outcomes.

scholarly journals NUCLEAR FUNCTION AND RELEASE OF IL-33

2014 ◽  
Vol 21 (03) ◽  
pp. 503-508
Author(s):  
Mousa Komai- Koma
Keyword(s):  
Signal Sequence ◽  
Cellular Interaction ◽  
Cell Phenotype ◽  
Nuclear Factor ◽  
T Helper ◽  
High Endothelial Venules ◽  
Interleukin 33 ◽  
T Helper 2 ◽  
St2 Receptor ◽  
Specific Ligand

Interleukin-33 (IL-33) is the most attractive novel cytokine identified as an IL-1family member. IL-33 was first named NF-HEV (nuclear factor from high endothelial venules), as itwas known to interact with nuclear chromatin although its exact intracellular functions are still tobe clarified. IL-33 is now recognized as the specific ligand for the orphan IL-1 receptor familymember ST2 and to be involved in polarization of T cells towards T helper 2-cell phenotype and inactivation of mast cells, basophils, eosinophils and natural killer cells. It is essential for IL-33 to beextracellularly released in order to bind to the ST2 receptor and consequently play a crucial role ininflammatory, infectious and autoimmune diseases. However, like the IL-1 family members, IL-1beta and IL-18, IL-33 mRNA is translated without a signal sequence for secretion. Additionally, IL-33 cannot be released by the processing and secretion mechanism shared by IL-1beta and IL-18as IL-33 is not a substrate of caspase-1 and does not require proteolysis for activation. In contrast,IL-33 can be inactivated by apoptotic caspases. Accordingly, IL-33 is proposed to be released asan alarmin from necrotic cells but deleted during apoptosis. Besides the known autocrine,paracrine mechanisms of cellular interaction with cytokines, release by necrotic cells is anotherpathway for a cytokine to display its function, which we suggest might be called 'necrocrine'.

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