A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo

Abstract

We describe a protein with the hallmarks of a chemokine, designated CXCL16, that is made by dendritic cells (DCs) in lymphoid organ T cell zones and by cells in the splenic red pulp. CXCL16 contains a transmembrane domain and both membrane-bound and soluble forms are produced. Naïve CD8 T cells, natural killer T cells and a subset of memory CD4 T cells bind CXCL16, and activated T cells migrated chemotactically to the soluble chemokine. By expression cloning, Bonzo (also known as STRL33 and TYMSTR) was identified as a CXCL16 receptor. CXCL16 may function in promoting interactions between DCs and CD8 T cells and in guiding T cell movements in the splenic red pulp. CXCL16 was also found in the thymic medulla and in some nonlymphoid tissues, indicating roles in thymocyte development and effector T cell trafficking.

The chemokine system: tuning and shaping by regulation of receptor expression and coupling in polarized responses

“…In vivo, CCL22/MDC was detected by in situ hybridization in mature DC and the protein is strongly produced by CD83 + cells in the skin of atopic dermatitis patients (45). CX3CL1/fractalkine and CXCL16, two chemokines present in both a membrane anchored and a soluble forms are produced by mature DC (46,47). CXCL13/ BLC is produced by follicular DC and germinal center DC and it is likely to play a role in interaction of DC with B and T lymphocytes (48).…”

Site‐directed mutagenesis of the chemokine receptor CXCR6 suggests a novel paradigm for interactions with the ligand CXCL16

“…Although typically produced as soluble, secreted proteins, the chemokine CXCL16 also exists as a membrane-bound form, consisting of a chemokine domain, a mucin-type stalk, a single-pass transmembrane (TM) domain and a cytoplasmic tail [2,3]. The mucin stalks serve to tether the chemokines to the cell membrane, while soluble versions of CXCL16 can be released by the action of membrane metalloproteinases [4,5].…”

“…Membrane-bound CXCL16 also facilitates the firm adhesion of cells expressing the G protein-coupled receptor CXCR6, such as activated T cells and NKT cells [10]. As a soluble chemokine, CXCL16 promotes chemotaxis via CXCR6, and serves as a chemoattractant for CXCR6 + T cells [2,3].…”

Human fractalkine mediates leukocyte adhesion but not capture under physiological shear conditions; a mechanism for selective monocyte recruitment

“…On the basis of the following characteristics, fractalkine has been hypothesized to act as a bona fide adhesion molecule, mediating leukocyte adhesion directly, rather than indirectly through selectins and integrins. First, fractalkine and the newly described CXCL16 [11] are the only chemokines identified to date that are bound directly to the cell membrane by a transmembrane region and mucinlike stalk [12][13][14]. As endothelial cells are primary producers of fractalkine [12,15], this chemokine would therefore have direct access to leukocytes in the circulation.…”