Specific time points could help direct the choice of therapy and ascertain whether a patient is responding to therapy in the case the mucosal levels of cytokine change. Moreover, determining the cytokine cell sources and mechanisms involved in the control of cytokine synthesis at the different stages of the disease could provide insight into the pathophysiology of CD. One limitation of this study is its relatively small sample size, despite a noticeable difference between CD patients and controls. However, this is the largest dataset available for patients with early CD lesions. Additionally, we should remain cautious wheninterpreting the physiologic implications of the Th1/Th2/Th17 imbalance in early and late CD because we analysed cytokines in whole biopsies and mucosal CD3+ T cells and not in purified CD4+ T cells. Thus, we cannot exclude the possibility that cytokines measured in our samples may derive from CD8+ T cells other than Th cells. Although we feel that prospective studies on larger numbers of patients will be needed to confirm data of this study, the cytokine expression results presented here provide evidence that there are potentially different immune mechanisms driving the early and late mucosal lesions in CD. A better understanding of such mechanisms could contribute to optimize therapeutic strategies in this disease.Author ContributionsConceived and designed the experiments: FZ GM. Performed the experiments: FZ I. Monteleone MS I. Marafini. Analyzed the data: FZ I. Monteleone GM. Contributed reagents/materials/analysis tools: EC MC SS LB. Wrote the paper: FZ FP GM.
Nischarin was first cloned from a mouse embryonic cDNA library and named by Alahari in 2000 [1]. In mouse Nischarin gene is found on chromosome 14, whereas in rat it is found on chromosome 16. The homology on the amino acid between mouse and rat is as much as 93 , suggesting the functional homology between the two isoforms. Nischarin interacts directly with integrin a5 and inhibits cell motility by affecting the signaling of the cytoskeleton regulated by Rho GTPases [2,3,4,5]. It inhibits the Rac1 signaling pathway by p21-activated 1655472 kinase (PAK)dependent and PAK-independent mechanisms [6], and negatively modulates the LIMK/cofilin pathway [5], resulting in decreased cell motility. Recently, Nischarin was reported to be a suppressor in breast cancer progression by regulating integrin a5 expression and the downstream signaling, including FAK phosphorylation and Rac activation [7]. The Rho GTPase family plays important roles in many cellular functions, such as proliferation, apoptosis, migration, and gene expression, by regulating actin dynamics [8,9]. In the nervous system, members of the Rho GTPase family are also actively involved in vital cellular processes, including morphological plasticity during neuronal polarization, migration and division [10], the formation of growth cones during axonal generation or regeneration [11,12,13], malformation of dendritic spines in mental Emixustat (hydrochloride) retardation [14,15,16], and the development of brain tumors [9,17]. Any factor in the nervous system that regulates P7C3 site thedownstream signaling cascade of Rho GTPase is likely to contribute to the above processes. Nischarin inhibits cancer cell migration by regulating the Rac1PAK-LIMK pathway, one of the key downstream pathways of Rho GTPase [2,6]. Thus, Nischarin is a possible candidate to play a crucial role in the brain. However, little is known about the distribution and function of Nisch.Specific time points could help direct the choice of therapy and ascertain whether a patient is responding to therapy in the case the mucosal levels of cytokine change. Moreover, determining the cytokine cell sources and mechanisms involved in the control of cytokine synthesis at the different stages of the disease could provide insight into the pathophysiology of CD. One limitation of this study is its relatively small sample size, despite a noticeable difference between CD patients and controls. However, this is the largest dataset available for patients with early CD lesions. Additionally, we should remain cautious wheninterpreting the physiologic implications of the Th1/Th2/Th17 imbalance in early and late CD because we analysed cytokines in whole biopsies and mucosal CD3+ T cells and not in purified CD4+ T cells. Thus, we cannot exclude the possibility that cytokines measured in our samples may derive from CD8+ T cells other than Th cells. Although we feel that prospective studies on larger numbers of patients will be needed to confirm data of this study, the cytokine expression results presented here provide evidence that there are potentially different immune mechanisms driving the early and late mucosal lesions in CD. A better understanding of such mechanisms could contribute to optimize therapeutic strategies in this disease.Author ContributionsConceived and designed the experiments: FZ GM. Performed the experiments: FZ I. Monteleone MS I. Marafini. Analyzed the data: FZ I. Monteleone GM. Contributed reagents/materials/analysis tools: EC MC SS LB. Wrote the paper: FZ FP GM.
Nischarin was first cloned from a mouse embryonic cDNA library and named by Alahari in 2000 [1]. In mouse Nischarin gene is found on chromosome 14, whereas in rat it is found on chromosome 16. The homology on the amino acid between mouse and rat is as much as 93 , suggesting the functional homology between the two isoforms. Nischarin interacts directly with integrin a5 and inhibits cell motility by affecting the signaling of the cytoskeleton regulated by Rho GTPases [2,3,4,5]. It inhibits the Rac1 signaling pathway by p21-activated 1655472 kinase (PAK)dependent and PAK-independent mechanisms [6], and negatively modulates the LIMK/cofilin pathway [5], resulting in decreased cell motility. Recently, Nischarin was reported to be a suppressor in breast cancer progression by regulating integrin a5 expression and the downstream signaling, including FAK phosphorylation and Rac activation [7]. The Rho GTPase family plays important roles in many cellular functions, such as proliferation, apoptosis, migration, and gene expression, by regulating actin dynamics [8,9]. In the nervous system, members of the Rho GTPase family are also actively involved in vital cellular processes, including morphological plasticity during neuronal polarization, migration and division [10], the formation of growth cones during axonal generation or regeneration [11,12,13], malformation of dendritic spines in mental retardation [14,15,16], and the development of brain tumors [9,17]. Any factor in the nervous system that regulates thedownstream signaling cascade of Rho GTPase is likely to contribute to the above processes. Nischarin inhibits cancer cell migration by regulating the Rac1PAK-LIMK pathway, one of the key downstream pathways of Rho GTPase [2,6]. Thus, Nischarin is a possible candidate to play a crucial role in the brain. However, little is known about the distribution and function of Nisch.
