Human CSF1 peptide

Long noncoding RNA (lncRNA) are non-protein-coding transcripts greater than 200 nucleotides that regulate gene expression. The field of transcriptomics is only beginning to understand the role of lncRNA in host defense. Little is known about the role of lncRNA in the response to infection by intracellular pathogens such as Toxoplasma gondii. Using a microarray, we examined the differential expression of 35,923 lncRNAs and 24,881 mRNAs in mouse bone-marrow-derived macrophages during infection with high-and low-virulence T. gondii strains. We found that 1,522 lncRNA molecules were differentially regulated during infection with the high-virulence Type I strain, versus 528 with the less-virulent Type II strain. Of these lncRNAs, 282 were co-regulated with a nearby or overlapping mRNA-including approximately 60 mRNAs with immune-related functions. We validated the microarray for 4 lncRNAs and 4 mRNAs using qRT-PCR. Using deletion strains of T. gondii, we found that the secretory kinase ROP16 controls upregulation of lncRNAs Csf1-lnc and Socs2-lnc, demonstrating that the parasite directly manipulates host lncRNA expression. Given the number of regulated lncRNAs and the magnitude of the expression changes, we hypothesize that these molecules constitute both an additional regulatory layer in the host response to infection and a target for manipulation by T. gondii.

Pigmented villonodular synovitis (PVNS), alternatively known as diffuse-type tenosynovial giant cell tumor (D-TGCT), is a rare joint disease tumor affecting young adults. Standard management requires iterative surgery, which may significantly impact quality of life. The molecular hallmark is a chromosomal translocation resulting in the fusion of an isotype of collagen with colony-stimulating factor 1 (CSF1) by the tumor cell component. This leads to an overproduction of the cytokine and the recruitment of CSF1-receptor (CSF1R)-expressing macrophages, eventually forming a locally destructive proliferation. TGCT is therefore considered as a neoplastic proliferation, locally aggressive and very rarely metastatic. CSF1R inhibitors have the potential to inhibit this pathogenetic loop, and are currently under investigation in several clinical trials. These inhibitors include small molecules like imatinib, nilotinib and pexidartinib, and monoclonal antibodies such as emactuzumab, MCS-110 and FPA-008. Preliminary efficacy data suggests that these drugs have the potential to modify the current management of D-TGCT. As CSF1 is also implicated in protumoral macrophage polarization, CSF1R inhibitors are also tested in combination with other immunotherapies in a wide variety of solid tumors. This review aims to describe the future management of D-TGCT in the era of CSF1R inhibitors.