CD9 Tetraspanin: A New Pathway for the Regulation of Inflammation?

Abstract

CD9 belongs to the tetraspanin superfamily. Depending on the cell type and associated molecules, CD9 has a wide variety of biological activities such as cell adhesion, motility, metastasis, growth, signal transduction, differentiation, and sperm–egg fusion. This review focuses on CD9 expression by hematopoietic cells and its role in modulating cellular processes involved in the regulation of inflammation. CD9 is functionally very important in many diseases and is involved either in the regulation or in the mediation of the disease. The role of CD9 in various diseases, such as viral and bacterial infections, cancer and chronic lung allograft dysfunction, is discussed. This review focuses also on its interest as a biomarker in diseases. Indeed CD9 is primarily known as a specific exosome marker however, its expression is now recognized as an anti-inflammatory marker of monocytes and macrophages. It was also described as a marker of murine IL-10-competent Breg cells and IL-10-secreting CD9+ B cells were associated with better allograft outcome in lung transplant patients, and identified as a new predictive biomarker of long-term survival. In the field of cancer, CD9 was both identified as a favorable prognostic marker or as a predictor of metastatic potential depending on cancer types. Finally, this review discusses strategies to target CD9 as a therapeutic tool. Because CD9 can have opposite effects depending on the situation, the environment and the pathology, modulating CD9 expression or blocking its effects seem to be a new promising therapeutic strategy.

B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role

“…We found that both exosome groups have exosome markers such as CD9 but TSG101 was only found in B7-H3 OE exosomes. CD9 is a tetraspanin, widely considered an exosome marker in various cell types including cancer cells [ 5 , 27 , 28 , 29 ]. TSG101 is an important component of the ESCRT-0 complex that promotes exosome secretion.…”

Tspan8-Tumor Extracellular Vesicle-Induced Endothelial Cell and Fibroblast Remodeling Relies on the Target Cell-Selective Response

“…CD81 complexes on DC, but also T cells account for uptake by hematopoietic cells, Tspan8-α6β4 for uptake by lung fibroblasts and Tspan8-α4/α5 for uptake by EC. Tspan8, CD151, CD9, and CD181 also contribute to uptake by several tumors [46,50,[97][98][99]. Though not essentially required, target cell tetraspanin webs can assist TEX uptake [27], where Fb and EC express CD81, Tspan31, Tspan4, and above all CD63 at a high level.…”

Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F

“…In addition, it regulates cell-cell fusion events in myoblasts (Tachibana & Hemler, 1999;Charrin et al, 2013), osteoclasts (Ishii et al, 2006), macrophages (Takeda et al, 2003), and sperm-egg cells (Boucheix, 2000;Kaji et al, 2000). Besides its physiological functions, CD9 is widely associated with diseases: both the up-regulation and down-regulation of CD9 are linked with poor prognosis in several types of cancer, such as melanoma, leukemia, and gastric, lung, breast, colon, and prostate malignancies (Brosseau et al, 2018). Moreover, CD9 modulates HIV-1-induced membrane fusion (Gordón-Alonso et al, 2006) and promotes MERS coronavirus entry by clustering host-cell receptors and proteases (Earnest et al, 2017;Florin & Lang, 2018).…”