Secretion of inflammatory factors from chondrocytes by layilin signaling
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Authors: Asano, Kota; Arito, Mitsumi; Kurokawa, Manae S.; Omoteyama, Kazuki; Okamoto, Kazuki; Suematsu, Naoya; Yudoh, Kazuo; Nakamura, Hiroshi; Beppu, Moroe; Kato, Tomohiro
Abstract
Layilin (LAYN) is thought to be involved in reorganization of cytoskeleton structures, interacting with merlin, radixin, and talin. Also, LAYN is known to be one of the receptors for hyaluronic acid (HA). In rheumatoid arthritis (RA), inflammatory cytokines like tumor necrosis factor alpha (TNF-alpha) have been known to play pathological roles. HA with low molecular weight is speculated to exacerbate inflammation in RA. In this context, differences of quantity and functions of HA receptors would affect the severity of inflammation in RA. Chondrocytes, which play critical roles in maintaining articular cartilage and are affected in RA, express at least kinds of HA receptors like CD44 and LAYN. However, roles and regulation of LAYN in articular chondrocytes have been poorly understood. To clarify regulation of LAYN in chondrocytes, we here investigated whether TNF-alpha affected expression levels of LAYN in human articular chondrocytes. Next, to clarify LAYN-specific roles in chondrocytes, we investigated whether binding of antibodies to the extracellular domain of LAYN affected secretion of inflammatory cytokines using a chondrosarcoma cell line. As a result, we found that TNF-alpha up-regulated expression levels of LAYN in the chondrocytes. Further, the LAYN signaling was found to enhance secretion of inflammatory factors, IL-8 and complement5 (C5)/C5a, from the cells. Our results indicate that LAYN would be involved in the enhancement of inflammation and degradation of cartilage in joint diseases such as RA and OA. (C) 2014 Elsevier Inc. All rights reserved.
Understanding tumor-infiltrating lymphocytes by single cell RNA sequencing
ADVANCES IN IMMUNOLOGY IN CHINA, PT A, VOL 144
Authors: Ren, Xianwen; Zhang, Zemin
Abstract
The clinical success of immune checkpoint blockade provides great hope for curing cancers. However, the patient responses are not even. Precise understanding of tumor immunity is necessary to improving the current cancer immunotherapies and to developing new treatment options. Here we applied full-length single cell RNA-seq (scRNA-seq) to three cancer types and provide a comprehensive single T cell data resource for understanding various characteristics of tumor-infiltrating T cells. We also developed an analytical framework named as STARTRAC to quantitatively characterize the dynamic properties of various T cell subsets including tissue preference, clonal expansion, migration, and state transitions from the scRNA-seq snapshots of tumor immune microenvironments. Conserved and cancer type-specific T cell subsets and developmental patterns were revealed, and detailed molecular portrait of the tumor immunity-relevant T cell clusters were provided, shedding lights into the cellular and molecular mechanisms underlying the composition, heterogeneity, and formation of tumor immune microenvironments. Important genes such as LAYN and IGFLR1 also provided new options for future development of cancer therapeutics.