A loss of telocytes accompanies fibrosis of multiple organs in systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a complex connective tissue disease characterized by fibrosis of the skin and various internal organs. In SSc, telocytes, a peculiar type of stromal (interstitial) cells, display severe ultrastructural damages and are progressively lost from the clinically affected skin. The aim of the present work was to investigate the presence and distribution of telocytes in the internal organs of SSc patients. Archival paraffin-embedded samples of gastric wall, myocardium and lung from SSc patients and controls were collected. Tissue sections were stained with Masson's trichrome to detect fibrosis. Telocytes were studied on tissue sections subjected to CD34 immunostaining. CD34/CD31 double immunofluorescence was performed to unequivocally differentiate telocytes (CD34-positive/CD31-negative) from vascular endothelial cells (CD34-positive/CD31-positive). Few telocytes entrapped in the fibrotic extracellular matrix were found in the muscularis mucosae and submucosa of SSc gastric wall. In the muscle layers and myenteric plexus, the network of telocytes was discontinuous or even completely absent around smooth muscle cells and ganglia. Telocytes were almost completely absent in fibrotic areas of SSc myocardium. In SSc fibrotic lung, few or no telocytes were observed in the thickened alveolar septa, around blood vessels and in the interstitial space surrounding terminal and respiratory bronchioles. In SSc, the loss of telocytes is not restricted to the skin, but it is a widespread process affecting multiple organs targeted by the fibrotic process. As telocytes are believed to be key players in the regulation of tissue/organ homoeostasis, our data suggest that telocyte loss might have important pathophysiological implications in SSc.

Telocytes in normal and keratoconic human cornea: an immunohistochemical and transmission electron microscopy study

“…In addition, we found that in the normal cornea, TC establish homocellular contacts formed by gap junctions, highly specialized membrane structures which allow the exchange of small molecular mediators involved in intercellular signalling and thus contributing to the maintenance of tissue homoeostasis 38, 39. As suggested in other pathologies 23, 25, 26, 27, 28, 29, the reduction and loss of TC might therefore contribute to the altered organization of the ECM ultimately resulting into corneal dysfunction in keratoconus.…”

“…It is commonly believed that TC may play an important role in driving organ development and contributing to the maintenance of local tissue homoeostasis and, hence, TC damage and dysfunction may occur in several disorders 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 52, 53. In this context, we herein demonstrate that the normal morphological features and distribution of TC are severely compromised within the corneal stromal compartment in keratoconic pathology.…”

“…Moreover, this peculiar stromal cell type is being increasingly implicated in a wide range of pathologies with potential applications in regenerative medicine 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36. Telocyte possess unique ultrastructural features consisting of a small cell body and extremely long and thin prolongations, termed telopodes, displaying a moniliform aspect characterized by the alternation of thin segments (called podomers) and small dilated regions (called podoms) accommodating mitochondria, endoplasmic reticulum cisternae and caveolae 11, 12, 37.…”

Interstitial lung disease in systemic sclerosis: where do we stand?

“…A recent study has shown loss of telocytes in the gastric wall, myocardium and lung of SSc patients, suggesting that this loss may be implicated in the pathogenesis of fibrosis [11]. Recently, elevated levels of interleukin (IL)-33 have been correlated with the severity of skin and lung fibrosis [12].…”

Ultrastructural identification of telocytes in the muscularis of chicken ileum

“…TCs have been described in the interstitium of certain parenchimatous organs in mammals (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) and, although ICCs have been identified in the digestive tract of turkeys (23) and in the intestine of chickens (24), the presence of ICLCs or TCs in the digestive system of the chicken remains unclear. In addition, Cantarero Carmona et al (25) described TCs at the intestinal level, in the lamina propria of rat duodenum; however, to the best of our knowledge, studies on TCs in the intestinal muscularis have not previously been conducted.…”