CCR7 is involved in the migration of neutrophils to lymph nodes

Abstract

Increasing evidence suggests that neutrophils may participate in the regulation of adaptive immune responses, and can reach draining lymph nodes and crossprime naive T cells. The aim of this study was to identify the mechanism(s) involved in the migration of neutrophils to the draining lymph nodes. We demonstrate that a subpopulation of human and mouse neutrophils express CCR7. CCR7 is rapidly expressed at the membrane upon stimulation. In vitro, stimulated human neutrophils migrate in response to the CCR7 ligands CCL19 and CCL21. In vivo, injection of complete Freund adjuvant induces a rapid recruitment of neutrophils to the lymph nodes in wild-type mice but not in Ccr7 ؊/؊ mice. Moreover, intradermally injected interleukin-17-and granulocyte-macrophage colonystimulating factor-stimulated neutrophils from wild-type mice, but not from Ccr7 ؊/؊ mice, migrate to the draining lymph nodes. These results identify CCR7 as a chemokine receptor involved in the migration of neutrophils to the lymph nodes. IntroductionPolymorphonuclear neutrophils are the most abundant immune cells in human blood (60% of leukocytes). Every day, 10 11 neutrophils transit through the adult human circulation. 1 They are the first type of leukocytes recruited at the site of infection, where they represent the major infiltrating cells. Their migration and subsequent activation are controlled by chemokines and cytokines such as chemokine (C-X-C motif) ligand 8 (CXCL8) and tumor necrosis factor-␣ (TNF-␣). At the inflammatory site, microorganisms are phagocytosed by neutrophils, destroyed via oxygendependent or oxygen-independent mechanisms, or sequestered in extracellular traps. 1,2 Neutrophils also contain an important arsenal of microbicidal mediators. 3 Neutrophils are short-lived, terminally differentiated cells that have long been considered to be the prototypic innate immune cells and to have a restricted number of properties. 4,5 Nevertheless, recent studies have shown that the biologic properties of neutrophils are more complicated than was previously thought. Neutrophils exhibit characteristic features classically dedicated to professional antigen-presenting cells. 6,7 Under certain circumstances, neutrophils display a dendritic cell (DC)-like phenotype, as evidenced by the expression of the DC markers CD83, CD80, CD86, and major histocompatibility complex II (MHC-II) molecules. Neutrophils may present antigens in an MHC-II-dependent manner and induce the proliferation of antigen-specific T cells. [6][7][8] More recently, we reported that neutrophils cross-prime naive CD8 ϩ T lymphocytes. 9 Finally, neutrophils may also influence the polarization of antigen-specific T-cell responses. [10][11][12] Interestingly, previous studies have reported that, after the capture of antigens in the periphery, neutrophils may migrate to the lymph nodes. [13][14][15] In a murine model of Toxoplasma gondii infection, parasites are transported by neutrophils from the infection site to draining lymph nodes. 15 Similarly, after an injection of ovalbumin (O...

CCL21 (SLC) improves tumor protection by a DNA vaccine in a Her2/neu mouse tumor model

“…It has recently been shown that CCR7-mediated signals may also have a role for migration of natural killer cells and neutrophils. 27,28 Furthermore, it is largely unknown where the chemoattractant CCL21 mainly exerts its effects after i.m. administration: at the injection site or in afferent lymphatic vessels/secondary lymphatic tissue.…”

Changing world of neutrophils

“…In confocal microscopic studies neutrophils migrating with fluorescently labeled pathogen were observed in draining lymph vessels [1] and lymph nodes [21]. Moreover, the chemokine receptor CCR7 has been identified as a key player in directing neutrophil migration from the interstitium to the draining lymph nodes [6].…”

Changes in gene expression of CXCR4, CCR7 and BCL2 after treatment of breast cancer cells with saponin extract from Tribulus terrestris

“…Increased levels of CCR7 have been found in a number of tumor types, one of which is breast cancer [35][36][37]. As expression of CCR7 is reportedly correlated with lymphatic metastasis and poor prognosis in breast cancers, it could be a good therapeutic target in breast cancer therapy [38].…”