scholarly journals Mast Cells in Liver Fibrogenesis

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1429 ◽  
Author(s):  
Ralf Weiskirchen ◽  
Steffen K. Meurer ◽  
Christian Liedtke ◽  
Michael Huber

Mast cells (MCs) are immune cells of the myeloid lineage that are present in the connective tissue throughout the body and in mucosa tissue. They originate from hematopoietic stem cells in the bone marrow and circulate as MC progenitors in the blood. After migration to various tissues, they differentiate into their mature form, which is characterized by a phenotype containing large granules enriched in a variety of bioactive compounds, including histamine and heparin. These cells can be activated in a receptor-dependent and -independent manner. Particularly, the activation of the high-affinity immunoglobulin E (IgE) receptor, also known as FcεRI, that is expressed on the surface of MCs provoke specific signaling cascades that leads to intracellular calcium influx, activation of different transcription factors, degranulation, and cytokine production. Therefore, MCs modulate many aspects in physiological and pathological conditions, including wound healing, defense against pathogens, immune tolerance, allergy, anaphylaxis, autoimmune defects, inflammation, and infectious and other disorders. In the liver, MCs are mainly associated with connective tissue located in the surrounding of the hepatic arteries, veins, and bile ducts. Recent work has demonstrated a significant increase in MC number during hepatic injury, suggesting an important role of these cells in liver disease and progression. In the present review, we summarize aspects of MC function and mediators in experimental liver injury, their interaction with other hepatic cell types, and their contribution to the pathogenesis of fibrosis.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4684-4684
Author(s):  
Raita Araki ◽  
Hideaki Maeba ◽  
Rie Kuroda ◽  
Toshihiro Fujiki ◽  
Shintaro Mase ◽  
...  

Abstract Abstract 4684 Mast cells have long been known as effector cells in the various IgE-mediated allergic responses. However, recent studies demonstrated that mast cells play various roles in immune reactions in coordination with other immune cells. That is, mast cells exert pro-inflammatory or anti-inflammatory effects depending on the situation. In addition, mast cells have association with tumor development. In allogeneic hematopoietic stem cell transplantation (HSCT), only a few have reported that the numbers of mast cells were correlated with the severity of acute GVHD in the skin. However, exact role of mast cells in GVHD remains unclear. With the purpose of potential application of mast cells in a clinical HSCT for GVHD, mixed lymphocyte reaction (MLR) was performed to clarify whether mast cells impaired the alloreaction or not. To generate bone marrow derived cultured mast cells (BMCMCs), BM cells from mice were incubated in complete RPMI containing IL-3 for 6 weeks. As shown in the figure, we showed that MLR was strongly inhibited when BMCMCs from the stimulator strain were added to the coculture (Stimulator (S): DCs obtained from C57BL/6, Responder (R): splenocytes from Balb/c, BMCMCs from C57BL/6). Next, when BMCMCs from the responder strain were added to the coculture, MLR was also suppressed (S: DCs obtained from C57BL/6, R: splenocytes from Balb/c, BMCMCs from Balb/c). In conclusion, mast cells suppressed lymphocyte proliferation induced by allo-DCs in an MHC-independent manner. Just like mesenchymal stem cells, cell therapy utilizing cultured mast cells may reduce GVHD severity. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Vol 22 (7) ◽  
pp. 3649
Author(s):  
Patricia Ramos-Ramírez ◽  
Omar Tliba

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRβ, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRβ has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRβ actions are restricted to its dominant-negative effects on GRα-mediated responses, GRβ has been shown to have intrinsic activities and “directly” regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRβ has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRβ-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRβ and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.


1984 ◽  
Vol 62 (6) ◽  
pp. 734-737 ◽  
Author(s):  
F. Shanahan ◽  
J. A. Denburg ◽  
J. Bienenstock ◽  
A. D. Befus

Increasing evidence for the existence of inter- and intra-species mast cell heterogeneity has expanded the potential biological role of this cell. Early studies suggesting that mast cells at mucosal sites differ morphologically and histochemically from connective tissue mast cells have been confirmed using isolated intestinal mucosal mast cells in the rat and more recently in man. These studies also established that mucosal mast cells are functionally distinct from connective tissue mast cells. Thus, mucosal and connective tissue mast cells differ in their responsiveness to a variety of mast cell secretagogues and antiallergic agents. Speculation about the therapeutic use of antiallergic drugs in disorders involving intestinal mast cells cannot, therefore, be based on extrapolation from studies of their effects on mast cells from other sites. Regulatory mechanisms for mast cell secretion may also be heterogeneous since mucosal mast cells differ from connective tissue mast cells in their response to a variety of physiologically occurring regulatory peptides. The development of techniques to purify isolated mast cell sub-populations will facilitate future analysis of the biochemical basis of the functional heterogeneity of mast cells.


Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 667
Author(s):  
Meera Krishnan ◽  
Sahil Kumar ◽  
Luis Johnson Kangale ◽  
Eric Ghigo ◽  
Prasad Abnave

Adult stem cells (ASCs) are the undifferentiated cells that possess self-renewal and differentiation abilities. They are present in all major organ systems of the body and are uniquely reserved there during development for tissue maintenance during homeostasis, injury, and infection. They do so by promptly modulating the dynamics of proliferation, differentiation, survival, and migration. Any imbalance in these processes may result in regeneration failure or developing cancer. Hence, the dynamics of these various behaviors of ASCs need to always be precisely controlled. Several genetic and epigenetic factors have been demonstrated to be involved in tightly regulating the proliferation, differentiation, and self-renewal of ASCs. Understanding these mechanisms is of great importance, given the role of stem cells in regenerative medicine. Investigations on various animal models have played a significant part in enriching our knowledge and giving In Vivo in-sight into such ASCs regulatory mechanisms. In this review, we have discussed the recent In Vivo studies demonstrating the role of various genetic factors in regulating dynamics of different ASCs viz. intestinal stem cells (ISCs), neural stem cells (NSCs), hematopoietic stem cells (HSCs), and epidermal stem cells (Ep-SCs).


2007 ◽  
Vol 204 (2) ◽  
pp. 253-258 ◽  
Author(s):  
Zoulfia Allakhverdi ◽  
Michael R. Comeau ◽  
Heidi K. Jessup ◽  
Bo-Rin Park Yoon ◽  
Avery Brewer ◽  
...  

Compelling evidence suggests that the epithelial cell–derived cytokine thymic stromal lymphopoietin (TSLP) may initiate asthma or atopic dermatitis through a dendritic cell–mediated T helper (Th)2 response. Here, we describe how TSLP might initiate and aggravate allergic inflammation in the absence of T lymphocytes and immunoglobulin E antibodies via the innate immune system. We show that TSLP, synergistically with interleukin 1 and tumor necrosis factor, stimulates the production of high levels of Th2 cytokines by human mast cells (MCs). We next report that TSLP is released by primary epithelial cells in response to certain microbial products, physical injury, or inflammatory cytokines. Direct epithelial cell–mediated, TSLP-dependent activation of MCs may play a central role in “intrinsic” forms of atopic diseases and explain the aggravating role of infection and scratching in these diseases.


Author(s):  
L. V. Antipova ◽  
S. A. Storublevtsev ◽  
A. A. Getmanova

In the process of life of the body continuously consumed nutrients that perform plastic and energy functions. The source of nutrients is a variety of foods, consisting of a complex of proteins, fats and carbohydrates, which in the process of digestion are converted into digestible substances. Collagen is the basis of connective tissue and binds the cells in the tissues, creates the frame of the whole body. The gastrointestinal tract, as a system of organs, is no exception and is designed process and extract nutrients from food. Most organs consist of connective tissue, accounting for 60–90% of their mass, which confirms its importance and the role of collagen in this regard can not be estimated. Collagen functions in the body are diverse, one of the main - part in digestion, the violation of which is the cause of diseases such as gastritis and ulcers. For the prevention and treatment of such diseases are very useful liquid collagen-containing food in the form of functional drinks. Developed and obtained in the experimental laboratory a variety of drinks on a collagen basis, with the use of additional broth with sea buckthorn pulp, tincture of dried chicory root powder and broth with the flesh of Jerusalem artichoke. An invaluable contribution to the therapeutic and preventive actions of all these components is proved not only scientifically, but also time-tested.


2020 ◽  
Author(s):  
Róbert Pálovics ◽  
Andreas Keller ◽  
Nicholas Schaum ◽  
Weilun Tan ◽  
Tobias Fehlmann ◽  
...  

Slowing or reversing biological ageing would have major implications for mitigating disease risk and maintaining vitality. While an increasing number of interventions show promise for rejuvenation, the effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplored. We performed single-cell RNA-sequencing on 13 organs to reveal cell type specific responses to young or aged blood in heterochronic parabiosis. Adipose mesenchymal stromal cells, hematopoietic stem cells, hepatocytes, and endothelial cells from multiple tissues appear especially responsive. On the pathway level, young blood invokes novel gene sets in addition to reversing established ageing patterns, with the global rescue of genes encoding electron transport chain subunits pinpointing a prominent role of mitochondrial function in parabiosis-mediated rejuvenation. Intriguingly, we observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it. Altogether, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity.


‘Infection and immunity’ considers the response of the body to pathogens, such as bacteria, viruses, prions, fungi, and parasites, which are discussed in terms of their nature, life cycle, and modes of infection. The role of the immune system in defence against infection is discussed, including innate and adaptive (acquired) immunity, antigens, the major histocompatibility complex, and the different cell types involved (antigen-presenting cells, T-cells, and B-cells). The mechanisms and cellular basis of inflammation are considered, as are post-infection repair mechanisms, and pathologies of the immune system such as hypersensitivity, autoimmunity and transplantations, and immunodeficiency (both primary and secondary to other diseases).


Blood ◽  
2020 ◽  
Vol 135 (23) ◽  
pp. 2049-2058 ◽  
Author(s):  
Christine R. Keenan ◽  
Nadia Iannarella ◽  
Gaetano Naselli ◽  
Naiara G. Bediaga ◽  
Timothy M. Johanson ◽  
...  

Abstract Loss of heterochromatin has been proposed as a universal mechanism of aging across different species and cell types. However, a comprehensive analysis of hematopoietic changes caused by heterochromatin loss is lacking. Moreover, there is conflict in the literature around the role of the major heterochromatic histone methyltransferase Suv39h1 in the aging process. Here, we use individual and dual deletion of Suv39h1 and Suv39h2 enzymes to examine the causal role of heterochromatin loss in hematopoietic cell development. Loss of neither Suv39h1 nor Suv39h2 individually had any effect on hematopoietic stem cell function or the development of mature lymphoid or myeloid lineages. However, deletion of both enzymes resulted in characteristic changes associated with aging such as reduced hematopoietic stem cell function, thymic involution and decreased lymphoid output with a skewing toward myeloid development, and increased memory T cells at the expense of naive T cells. These cellular changes were accompanied by molecular changes consistent with aging, including alterations in nuclear shape and increased nucleolar size. Together, our results indicate that the hematopoietic system has a remarkable tolerance for major disruptions in chromatin structure and reveal a role for Suv39h2 in depositing sufficient H3K9me3 to protect the entire hematopoietic system from changes associated with premature aging.


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