Considering the main studies on lung and heartClung transplantation an overall survival of 52C80% at 2?years is reported [87C90]. treatment strategies at our disposal to induce remission into three categories: high intensity (haematopoietic stem cell transplantation), medium intensity (CYC and RTX) Isoconazole nitrate and low intensity (azathioprine (AZA) and mycophenolate mofetil (MMF)). After obtaining remission, maintenance treatment with AZA or MMF should be started. In this review we explore new advances in the pathogenesis, diagnosis and treatment of SSc-ILD. Short abstract Early diagnosis of ILD is possible, and is mandatory to improve the prognosis of the disease http://ow.ly/P28JH The relevance of interstitial lung disease in systemic sclerosis Isoconazole nitrate Pulmonary disease in systemic sclerosis (SSc) mainly comprises interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). Over the past 40?years the SSc mortality rate has not changed significantly [1]. Nevertheless, while the frequency of deaths due to renal crisis has significantly decreased from 42% to 6%, the proportion of deaths due to ILD and PAH has increased [2]. In fact, ILD and PAH are the two main causes of death in SSc, accounting for 33% and 28% of deaths, respectively [2]. A European Scleroderma Trials and Research group (EUSTAR) analysis revealed, in a cohort of 3656 SSc patients, that ILD is present in 53% of cases with diffuse cutaneous SSc and in 35% of cases with limited cutaneous SSc [3]. Cumulative survival of SSc patients from diagnosis is 84.1% at 5?years and 74.9% at 10?years [4]. The reported survival of SSc-ILD patients is similar to that of patients without ILD at 5?years while it is significantly lower at 10?years. In fact, the survival of SSc-ILD patients is reported to be 29C69% at 10?years [5]. In early autopsy studies, up to 100% of patients have parenchymal involvement [4], as many as 90% of patients show interstitial abnormalities on high-resolution computed tomography (HRCT) [6], and 40C75% have changes in pulmonary function tests (PFTs) [7]. Considering the frequency of lung involvement in SSc and its impact on the prognosis, it is important to recognise patients with ILD early and treat them appropriately. Pathogenesis The pathogenesis of SSc-ILD is not yet fully understood. Three steps are considered to be involved: 1) persistent and repeated bouts of injury to endothelial cells, 2) activation of innate and adaptive immunity and 3) fibroblast recruitment/activation, which results in accumulation of extracellular matrix and scarring [8]. Still, the exact pathways and mechanisms are not clear and have been the object of recent studies. A pivotal role seems to be played by transforming growth factor (TGF)- which is secreted by platelets, monocytes/macrophages, T-cells and fibroblasts. The binding of TGF- to its Isoconazole nitrate receptor activates Smad-dependent and Smad-independent pathways, including the mitogen-activated protein kinases p38 and c-Jun N-terminal kinase, the lipid kinase phosphoinositol-3-kinase, the tyrosine kinase c-ABL, and the Rho-associated coiled-coil containing protein kinase [9]. Target genes of Smad-dependent TGF- signalling are type I collagen, plasminogen activator inhibitor, -smooth muscle actin and connective tissue growth factor. Toll-like receptor (TLR)4 is widely recognised as central to the innate immune response to Gram-negative bacteria, but it can also be activated by endogenous ligands generated by cellular injury, the autoimmune response and oxidative stress. In skin and lung biopsies DNM1 of SSc patients, increased expression of TLR4 has been demonstrated. TLR4 activation potentiates TGF- signalling and suppresses antifibrotic microRNA [10]. Telocytes are Isoconazole nitrate a peculiar type of stromal cell, which may have a role in the regulation of tissue homeostasis. A recent study has shown loss of telocytes in the gastric wall, myocardium and lung of SSc patients, suggesting that this loss may.