Subepithelial Mesenchymal Cells Research Articles

Patterning and folding of intestinal villi by active mesenchymal dewetting

Tissue folds are structural motifs critical to organ function. In the intestine, bending of a flat epithelium into a periodic pattern of folds gives rise to villi, finger-like protrusions that enable nutrient absorption. However, the molecular and mechanical processes driving villus morphogenesis remain unclear. Here, we identify an active mechanical mechanism that simultaneously patterns and folds the intestinal epithelium to initiate villus formation. At the cellular level, we find that PDGFRA+ subepithelial mesenchymal cells generate myosin II-dependent forces sufficient to produce patterned curvature in neighboring tissue interfaces. This symmetry-breaking process requires altered cell and extracellular matrix interactions that are enabled by matrix metalloproteinase-mediated tissue fluidization. Computational models, together with invitro and invivo experiments, revealed that these cellular features manifest at the tissue level as differences in interfacial tensions that promote mesenchymal aggregation and interface bending through a process analogous to the active dewetting of a thin liquid film.

Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members.

The protective and absorptive functions of the intestinal epithelium rely on differentiated enterocytes in the villi. The differentiation of enterocytes is orchestrated by sub-epithelial mesenchymal cells producing distinct ligands along the villus axis, in particular Bmps and Tgfβ. Here, we show that individual Bmp ligands and Tgfβ drive distinct enterocytic programs specific to villus zonation. Bmp4 is expressed from the centre to the upper part of the villus and activates preferentially genes connected to lipid uptake and metabolism. In contrast, Bmp2 is produced by villus tip mesenchymal cells and it influences the adhesive properties of villus tip epithelial cells and the expression of immunomodulators. Additionally, Tgfβ induces epithelial gene expression programs similar to those triggered by Bmp2. Bmp2-driven villus tip program is activated by a canonical Bmp receptor type I/Smad-dependent mechanism. Finally, we establish an organoid cultivation system that enriches villus tip enterocytes and thereby better mimics the cellular composition of the intestinal epithelium. Our data suggest that not only a Bmp gradient but also the activity of individual Bmp drives specific enterocytic programs.

HNF4α Acts as Upstream Functional Regulator of Intestinal Wnt3 and Paneth Cell Fate

The intestinal epithelium intrinsically renews itself exvivo via the proliferation of Lgr5+ intestinal stem cells, which is sustained by the establishment of an epithelial stem cell niche. Differentiated Paneth cells are the main source of epithelial-derived niche factor supplies and produce Wnt3 as an essential factor in supporting Lgr5+ stem cell activity in the absence of redundant mesenchymal Wnts. Maturation of Paneth cells depends on canonical Wnt signaling, but few transcriptional regulators have been identified to this end. The role of HNF4α in intestinal epithelial cell differentiation is considered redundant with its paralog HNF4γ. However, it is unclear whether HNF4α alone controls intrinsic intestinal epithelial cell growth and fate in the absence of a mesenchymal niche. We used transcriptomic analyses to dissect the role of HNF4α in the maintenance of jejunal epithelial culture when cultured exvivo as enteroids in the presence or absence of compensatory mesenchymal cells. HNF4α plays a crucial role in supporting the growth and survival of jejunal enteroids. Transcriptomic analyses revealed an autonomous function of HNF4α in Wnt3 transcriptional regulation and Paneth cell differentiation. We showed that Wnt3a supplementation or co-culture with intestinal subepithelial mesenchymal cells reversed cell death and transcriptional changes caused by the deletion of Hnf4a in jejunal enteroids. Our results support the intrinsic epithelial role of HNF4α in regulating Paneth cell homeostasis and intestinal epithelium renewal in the absence of compensatory Wnt signaling.

Mesenchymal-epithelial crosstalk shapes intestinal regionalisation via Wnt and Shh signalling

Organs are anatomically compartmentalised to cater for specialised functions. In the small intestine (SI), regionalisation enables sequential processing of food and nutrient absorption. While several studies indicate the critical importance of non-epithelial cells during development and homeostasis, the extent to which these cells contribute to regionalisation during morphogenesis remains unexplored. Here, we identify a mesenchymal-epithelial crosstalk that shapes the developing SI during late morphogenesis. We find that subepithelial mesenchymal cells are characterised by gradients of factors supporting Wnt signalling and stimulate epithelial growth in vitro. Such a gradient impacts epithelial gene expression and regional villus formation along the anterior-posterior axis of the SI. Notably, we further provide evidence that Wnt signalling directly regulates epithelial expression of Sonic Hedgehog (SHH), which, in turn, acts on mesenchymal cells to drive villi formation. Taken together our results uncover a mechanistic link between Wnt and Hedgehog signalling across different cellular compartments that is central for anterior-posterior regionalisation and correct formation of the SI.

Airway Wall Remodeling in Childhood Asthma—A Personalized Perspective from Cell Type-Specific Biology

Airway wall remodeling is a pathology occurring in chronic inflammatory lung diseases including asthma, chronic obstructive pulmonary disease, and fibrosis. In 2017, the American Thoracic Society released a research statement highlighting the gaps in knowledge and understanding of airway wall remodeling. The four major challenges addressed in this statement were: (i) the lack of consensus to define “airway wall remodeling” in different diseases, (ii) methodologic limitations and inappropriate models, (iii) the lack of anti-remodeling therapies, and (iv) the difficulty to define endpoints and outcomes in relevant studies. This review focuses on the importance of cell-cell interaction, especially the bronchial epithelium, in asthma-associated airway wall remodeling. The pathology of “airway wall remodeling” summarizes all structural changes of the airway wall without differentiating between different pheno- or endo-types of asthma. Indicators of airway wall remodeling have been reported in childhood asthma in the absence of any sign of inflammation; thus, the initiation event remains unknown. Recent studies have implied that the interaction between the epithelium with immune cells and sub-epithelial mesenchymal cells is modified in asthma by a yet unknown epigenetic mechanism during early childhood.

Bronchial thermoplasty in asthma: an exploratory histopathological evaluation in distinct asthma endotypes/phenotypes

BackgroundBronchial thermoplasty regulates structural abnormalities involved in airway narrowing in asthma. In the present study we aimed to investigate the effect of bronchial thermoplasty on histopathological bronchial structures in distinct asthma endotypes/phenotypes.MethodsEndobronchial biopsies (n = 450) were collected from 30 patients with severe uncontrolled asthma before bronchial thermoplasty and after 3 sequential bronchial thermoplasties. Patients were classified based on blood eosinophils, atopy, allergy and smoke exposure. Tissue sections were assessed for histopathological parameters and expression of heat-shock proteins and glucocorticoid receptor. Proliferating cells were determined by Ki67-staining.ResultsIn all patients, bronchial thermoplasty improved asthma control (p < 0.001), reduced airway smooth muscle (p = 0.014) and increased proliferative (Ki67 +) epithelial cells (p = 0.014). After bronchial thermoplasty, airway smooth muscle decreased predominantly in patients with T2 high asthma endotype. Epithelial cell proliferation was increased after bronchial thermoplasty in patients with low blood eosinophils (p = 0.016), patients with no allergy (p = 0.028) and patients without smoke exposure (p = 0.034).In all patients, bronchial thermoplasty increased the expression of glucocorticoid receptor in epithelial cells (p = 0.018) and subepithelial mesenchymal cells (p = 0.033) and the translocation of glucocorticoid receptor in the nucleus (p = 0.036). Furthermore, bronchial thermoplasty increased the expression of heat shock protein-70 (p = 0.002) and heat shock protein-90 (p = 0.001) in epithelial cells and decreased the expression of heat shock protein-70 (p = 0.009) and heat shock protein-90 (p = 0.002) in subepithelial mesenchymal cells. The effect of bronchial thermoplasty on the expression of heat shock proteins -70 and -90 was distinctive across different asthma endotypes/phenotypes.ConclusionsBronchial thermoplasty leads to a diminishment of airway smooth muscle, to epithelial cell regeneration, increased expression and activation of glucocorticoid receptor in the airways and increased expression of heat shock proteins in the epithelium. Histopathological effects appear to be distinct in different endotypes/phenotypes indicating that the beneficial effects of bronchial thermoplasty are achieved by diverse molecular targets associated with asthma endotypes/phenotypes.

MRISCs protect colonic stem cells from inflammatory damage

Increasing evidence suggest functional roles of subepithelial mesenchymal niche cells in maintaining intestinal stem cells and in modulating the pathogenesis of various intestinal diseases in mammals. A recent study reported the discovery of a new population of stromal cells in mice termed MAP3K2-Regulated Intestinal Stromal Cells (MRISCs); these cells reside at the base of colonic crypt and function to protect colonic stem cells during colonic inflammation by expressing the Wnt agonist R-spondin1 (Rspo1).

A FoxL1-CreERT-2A-tdTomato Mouse Labels Subepithelial Telocytes.

A FoxL1-CreERT-2A-tdTomato Mouse Labels Subepithelial Telocytes.

Histological aspects of limbal stem cell transplantation

AbstractMaintenance and regeneration of the corneal epithelium relies on unipotent progenitor cells at the corneoscleral limbus, which are regulated by extrinsic factors from their local microenvironment, the stem cell niche. The postulated limbal niche is an anatomically protected site of intimate epithelial‐mesenchymal interaction and is highly vascularised, innervated, pigmented due to intraepithelial melanocytes. In addition, the limbal niche is infiltrated with immune cells, and supported by a specialized extracellular matrix as well as subepithelial mesenchymal cells emitting soluble signals. For ex vivo expansion and transplantation, limbal stem cells are unfavourably removed from their niche. This lecture outlines our current understanding and novel findings regarding the structural and molecular composition of the limbal niche including specific matrix components, cell‐matrix‐ and cell‐cell adhesion molecules, and niche cell populations, which are involved in stem cell regulation through multiple signalling pathways. This lecture also provides an overview of current tissue‐engineering approaches for corneal surface regeneration that aim at incorporating specific niche components, such as matrix proteins, growth and signalling factors, or putative niche cells, into the culture systems in order to support maintenance of stemness and to improve the therapeutic use of limbal stem cell transplantation.

TGF-β Upregulated Mitochondria Mass through the SMAD2/3→C/EBPβ→PRMT1 Signal Pathway in Primary Human Lung Fibroblasts.

Tissue remodeling of subepithelial mesenchymal cells is a major pathologic condition of chronic obstructive pulmonary disease and asthma. Fibroblasts contribute to fibrotic events and inflammation in both airway diseases. Recent mechanistic studies established a link between mitochondrial dysfunction or aberrant biogenesis leading to tissue remodeling of the airway wall in asthma. Protein arginine methyltransferase-1 (PRMT1) participated in airway wall remodeling in pulmonary inflammation. This study investigated the mechanism by which PRMT1 regulates mitochondrial mass in primary human airway wall fibroblasts. Fibroblasts from control or asthma patients were stimulated with TGF-β for up to 48 h, and the signaling pathways controlling PRMT1 expression and mitochondrial mass were analyzed. PRMT1 activity was suppressed by the pan-PRMT inhibitor AMI-1. The SMAD2/3 pathway was blocked by SB203580 and C/EBPβ by small interference RNA treatment. The data obtained from unstimulated cells showed a significantly higher basal expression of PRMT1 and mitochondrial markers in asthmatic compared with control fibroblasts. In all cells, TGF-β significantly increased the expression of PRMT1 through SMAD2/3 and C/EBPβ. Subsequently, PRMT1 upregulated the expression of the mitochondria regulators PGC-1α and heat shock protein 60. Both the inhibition of the SAMD2/3 pathway or PRMT1 attenuated TGF-β-induced mitochondrial mass and C/EBPβ and α-SMA expression. These findings suggest that the signaling sequence controlling mitochondria in primary human lung fibroblasts is as follows: TGF-β→SMAD2/3→C/EBPβ→PRMT1→PGC-1α. Therefore, PRMT1 and C/EBPβ present a novel therapeutic and diagnostic target for airway wall remodeling in chronic lung diseases.

GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells.

Wnt-β-catenin signalling plays a pivotal role in the homeostasis of the intestinal epithelium by promoting stem cell renewal1,2. In the small intestine, epithelial Paneth cells secrete Wnt ligands and thus adopt the function of the stem cell niche to maintain epithelial homeostasis3,4. It is unclear which cells comprise the stem cell niche in the colon. Here we show that subepithelial mesenchymal GLI1-expressing cells form this essential niche. Blocking Wnt secretion from GLI1-expressing cells prevents colonic stem cell renewal in mice: the stem cells are lost and, as a consequence, the integrity of the colonic epithelium is corrupted, leading to death. GLI1-expressing cells also play an important role in the maintenance of the small intestine, where they serve as a reserve Wnt source that becomes critical when Wnt secretion from epithelial cells is prevented. Our data suggest a mechanism by which the stem cell niche is adjusted to meet the needs of the intestine via adaptive changes in the number of mesenchymal GLI1-expressing cells.

Primordial odontogenic tumor: Subepithelial expression of Syndecan-1 and Ki-67 suggests origin during early odontogenesis.

Primordial odontogenic tumor (POT) is composed of variably cellular myxoid connective tissue, surrounded by cuboidal to columnar odontogenic epithelium resembling the inner epithelium of the enamel organ, which often invaginates into the underlying connective tissue. The tumor is delimited at least partially by a thin fibrous capsule. It derives from the early stages of tooth development. Syndecan-1 is a heparan sulfate proteoglycan that has a physiological role in several cellular functions, including maintenance of the epithelial architecture, cell-to-cell adhesion and interaction of cells with extracellular matrix, and with diverse growth factors, stimulating cell proliferation. Ki-67 is considered the gold standard as a cell proliferation marker. The aim of this study was to examine the expression of Syndecan-1 and Ki-67 proliferation index in POT and normal tooth germs to better understand the biological behavior of this tumor. Results showed that Syndecan-1 was more intensely expressed in subepithelial mesenchymal areas of POT, in a pattern that resembles the early stages of tooth development. The cell proliferation index (4.1%) suggests that POT is a slow growing tumor. Syndecan-1 expression in tooth germs in late cap and early bell stages was similar to POT, showing immunopositivity in subepithelial mesenchymal condensed areas. The immunohistochemical findings showed a pattern in which the population of subepithelial mesenchymal cells exhibited greater proliferative activity than the central portion of the dental papilla.

Epigallocatechin-3-gallate inhibits inflammation and epithelial‑mesenchymal transition through the PI3K/AKT pathway via upregulation of PTEN in asthma.

Asthma is a chronic disease associated with hyper-responsiveness, obstruction and remodeling of the airways. Epithelial-mesenchymal transition (EMT) has an important role in these alterations and may account for the accumulation of subepithelial mesenchymal cells, thus contributing to airway hyperresponsiveness and remodeling. Epigallo-catechin-3-gallate (EGCG), which is a type of polyphenol, is the most potent ingredient in green tea, and exhibits antibacterial, antiviral, antioxidative, anticancer and chemopreventive activities. Recently, numerous studies have investigated the protective effects of EGCG against asthma and other lung diseases. In the present study, the role of EGCG in ovalbumin (OVA)-challenged asthmatic mice was determined. In addition, the inhibitory effects of EGCG against transforming growth factor (TGF)-β1-induced EMT and migration of 16HBE cells, and the underlying mechanisms of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway, were investigated by immunofluorescence, Transwell, wound healing assay and western blot analysis, respectively. The results indicated that EGCG may suppress inflammation and inflammatory cell infiltration into the lungs of OVA-challenged asthmatic mice, and may also inhibit EMT via the PI3K/AKT signaling pathway through upregulating the expression of phosphatase and tensin homolog (PTEN) in vivo and in vitro. The present study also revealed the anti-migratory effects of EGCG in TGF-β1-induced 16HBE cells, thus suggesting it may reduce airway remodeling. The present study provides a novel insight into understanding the protective effects of EGCG on airway remodeling in asthma, and indicates that EGCG may be useful as an adjuvant therapy for bronchial asthma.

Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota

Immunoglobulin A (IgA) maintains a symbiotic equilibrium with intestinal microbes. IgA induction in the gut-associated lymphoid tissues (GALTs) is dependent on microbial sampling and cellular interaction in the subepithelial dome (SED). However it is unclear how IgA induction is predominantly initiated in the SED. Here we show that previously unrecognized mesenchymal cells in the SED of GALTs regulate bacteria-specific IgA production and diversify the gut microbiota. Mesenchymal cells expressing the cytokine RANKL directly interact with the gut epithelium to control CCL20 expression and microfold (M) cell differentiation. The deletion of mesenchymal RANKL impairs M cell-dependent antigen sampling and B cell-dendritic cell interaction in the SED, which results in a reduction in IgA production and a decrease in microbial diversity. Thus, the subepithelial mesenchymal cells that serve as M cell inducers have a fundamental role in the maintenance of intestinal immune homeostasis.

Wnt Ligands Secreted by Subepithelial Mesenchymal Cells Are Essential for the Survival of Intestinal Stem Cells and Gut Homeostasis.

Targeting of Wnt signaling represents a promising anti-cancer therapy. However, the consequences of systemically attenuating the Wnt pathway in an adult organism are unknown. Here, we globally prevent Wnt secretion by genetically ablating Wntless. We find that preventing Wnt signaling in the entire body causes mortality due to impaired intestinal homeostasis. This is caused by the loss of intestinal stem cells. Reconstitution of Wnt/β-catenin signaling via delivery of external Wnt ligands prolongs the survival of intestinal stem cells and reveals the essential roleof extra-epithelial Wnt ligands for the renewal of the intestinal epithelium. Wnt2b is a key extra-epithelial Wnt ligand capable of promoting Wnt/β-catenin signaling and intestinal homeostasis. Wnt2b is secreted by subepithelial mesenchymal cells that co-express either Gli1 or Acta2. Subepithelial mesenchymal cells expressing high levels of Wnt2b are predominantly Gli1 positive.

PDGF-BB induces PRMT1 expression through ERK1/2 dependent STAT1 activation and regulates remodeling in primary human lung fibroblasts

Tissue remodeling of sub-epithelial mesenchymal cells is a major pathology occurring in chronic obstructive pulmonary disease (COPD) and asthma. Fibroblasts, as a major source of interstitial connective tissue extracellular matrix, contribute to the fibrotic and inflammatory changes in these airways diseases. Previously, we described that protein arginine methyltransferase-1 (PRMT1) participates in airway remodeling in a rat model of pulmonary inflammation. In this study we investigated the mechanism by which PDGF-BB regulates PRMT1 in primary lung fibroblasts, isolated from human lung biopsies. Fibroblasts were stimulated with PDGF-BB for up-to 48h and the regulatory and activation of signaling pathways controlling PRMT1 expression were determined. PRMT1 was localized by immuno-histochemistry in human lung tissue sections and by immunofluorescence in isolated fibroblasts. PRMT1 activity was suppressed by the pan-PRMT inhibitor AMI1. ERK1/2 mitogen activated protein kinase (MAPK) was blocked by PD98059, p38 MAPK by SB203580, and STAT1 by small interference (si) RNA treatment. The results showed that PDGF-BB significantly increased PRMT1 expression after 1h lasting over 48h, through ERK1/2 MAPK and STAT1 signaling. The inhibition of ERK1/2 MAPK or of PRMT1 activity decreased PDGF-BB induced fibroblast proliferation, COX2 production, collagen-1A1 secretion, and fibronectin production. These findings suggest that PRMT1 is a central regulator of tissue remodeling and that the signaling sequence controlling its expression in primary human lung fibroblast is PDGF–ERK–STAT1. Therefore, PRMT1 presents a novel therapeutic and diagnostic target for the control of airway wall remodeling in chronic lung diseases.

Limbal stem cell niche – New insights into structural and molecular composition

SummaryMaintenance and regeneration of the corneal epithelium relies on unipotent progenitor cells at the corneoscleral limbus, which are regulated by extrinsic factors from their local microenvironment, the stem cell niche. The postulated limbal niche is an anatomically protected site of intimate epithelial‐mesenchymal interaction and is highly vascularised, innervated, pigmented due to intraepithelial melanocytes, infiltrated with immune cells, and supported by a specialized extracellular matrix as well as subepithelial mesenchymal cells emitting soluble signals. For ex vivo expansion and transplantation, limbal stem cells are unfavourably removed from their niche. This lecture outlines our current understanding and novel findings regarding the structural and molecular composition of the limbal niche including specific matrix components, cell‐matrix‐ and cell‐cell adhesion molecules, and niche cell populations, which are involved in stem cell regulation through multiple signalling pathways including the Hedgehog pathway. This lecture also provides an overview of current tissue‐engineering approaches for corneal surface regeneration that aim at incorporating specific niche components, such as matrix proteins, growth and signalling factors, or putative niche cells, into the culture systems in order to support maintenance of stemness and to improve the therapeutic use of limbal stem cell transplantation.

Gross and Microanatomical Studies on the Uterus of Japanese Quail (Coturnix japonica) During the Post-hatching Period with Special Emphasis on Sperm Host Gland

The quail acts as a model for recent experimental studies and its oviduct development is of special interest. This study was carried out on 61 adult female Japanese Quail (Coturnix japonica) collected from quail farms in Assiut and South Valley Universities in order to characterize the morphological features of the uterus during the post-hatching life. The process of development was consisted of three stages: undifferentiated, differentiated and adult stage. The undifferentiated stage began from day of hatching till 25-days old age and the oviduct was divided into cranial, middle and caudal parts. The caudal part (the future uterus and vagina) was represented by a simple wall of a single layer of simple columnar epithelial cells resting on subepithelial undifferentiated mesenchymal cells with many mitotic divisions. At 20 days old, the mucosa is thrown into distinct mucosal folds as well as the ciliated and secretory epithelial cells were first appeared at this age. At differentiated stage (from 30-40 days), the tubular glands began to develop and opened between the epithelial cells. The adult stage began from 50 days old and the luminal surface of the uterus was characterized by numerous long leaf-like folds. Also, the apical part of the cells showed positive reaction with PAS and Alcian blue. The tubular glands are filled with the secretion, which give positive reaction with PAS and Alcian blue. The uterovaginal junction lies between the uterus and the cranial part of the vagina, and contains the sperm host gland. This area showed transition of the mucosal folds from longitudinal folds of the uterus to complex interconnecting folds of the vagina. Many typical sperms with oval head and tail were inserted between the ciliated and microvillous surface epithelial cells of sperm host glands. This detailed anatomical and histological study of post-hatching development of uterus in quail will not only help to evaluate changes occurs during this critical period, but also will assist in understanding clearly the physiology of reproduction in quail.

Fstl1 Antagonizes BMP Signaling and Regulates Ureter Development

Bone morphogenetic protein (BMP) signaling pathway plays important roles in urinary tract development although the detailed regulation of its activity in this process remains unclear. Here we report that follistatin-like 1 (Fstl1), encoding a secreted extracellular glycoprotein, is expressed in developing ureter and antagonizes BMP signaling activity. Mouse embryos carrying disrupted Fstl1 gene displayed prominent hydroureter arising from proximal segment and ureterovesical junction defects. These defects were associated with significant reduction in ureteric epithelial cell proliferation at E15.5 and E16.5 as well as absence of subepithelial ureteral mesenchymal cells in the urinary tract at E16.5 and E18.5. At the molecular level, increased BMP signaling was found in Fstl1 deficient ureters, indicated by elevated pSmad1/5/8 activity. In vitro study also indicated that Fstl1 can directly bind to ALK6 which is specifically expressed in ureteric epithelial cells in developing ureter. Furthermore, Sonic hedgehog (SHH) signaling, which is crucial for differentiation of ureteral subepithelial cell proliferation, was also impaired in Fstl1-/- ureter. Altogether, our data suggest that Fstl1 is essential in maintaining normal ureter development by antagonizing BMP signaling.

Is there a regulatory role of immunoglobulins on tissue forming cells relevant in chronic inflammatory lung diseases?

Epithelial cells, fibroblasts and smooth muscle cells together form and give structure to the airway wall. These three tissue forming cell types are structure giving elements and participate in the immune response to inhaled particles including allergens and dust. All three cell types actively contribute to the pathogenesis of chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). Tissue forming cells respond directly to allergens through activated immunoglobulins which then bind to their corresponding cell surface receptors. It was only recently reported that allergens and particles traffic through epithelial cells without modification and bind to the immunoglobulin receptors on the surface of sub-epithelial mesenchymal cells. In consequence, these cells secrete pro-inflammatory cytokines, thereby extending the local inflammation. Furthermore, activation of the immunoglobulin receptors can induce proliferation and tissue remodeling of the tissue forming cells. New studies using anti-IgE antibody therapy indicate that the inhibition of immunoglobulins reduces the response of tissue forming cells. The unmeasured questions are: (i) why do tissue forming cells express immunoglobulin receptors and (ii) do tissue forming cells process immunoglobulin receptor bound particles? The focus of this review is to provide an overview of the expression and function of various immunoglobulin receptors.