The Chemokine Receptor CCR7 Uses Distinct Signaling Modules With Biased Functionality to Regulate Dendritic Cells.

Chemotaxis is a molecular mechanism that confers leukocytes the ability to detect gradients of chemoattractants. Chemokine receptors are well-known regulators of chemotaxis in leukocytes; however, they can regulate several other activities in these cells. This information has been often neglected, probably due to the paramount role of chemotaxis in the immune system and in biology.

Immunological Synapse Formation Induces Mitochondrial Clustering and Mitophagy in Dendritic Cells.

The immunological synapse (IS) is a superstructure formed during T cell activation at the zone of contact between T cells and dendritic cells (DCs). The IS includes specific molecular components in the T cell and DCs sides that may result in different functionality. Most of the studies on the IS have focused on the T cell side of this structure and, in contrast, the information available on the IS of DCs is sparse.

Macrophage-specific MHCII expression is regulated by a remote enhancer controlled by NFAT5.

MHCII in antigen-presenting cells (APCs) is a key regulator of adaptive immune responses. Expression of MHCII genes is controlled by the transcription coactivator CIITA, itself regulated through cell type-specific promoters. Here we show that the transcription factor NFAT5 is needed for expression of and MHCII in macrophages, but not in dendritic cells and other APCs.

Liver X Receptor Nuclear Receptors Are Transcriptional Regulators of Dendritic Cell Chemotaxis.

The liver X receptors (LXRs) are ligand-activated nuclear receptors with established roles in the maintenance of lipid homeostasis in multiple tissues. LXRs exert additional biological functions as negative regulators of inflammation, particularly in macrophages. However, the transcriptional responses controlled by LXRs in other myeloid cells, such as dendritic cells (DCs), are still poorly understood.

Beyond Chemoattraction: Multifunctionality of Chemokine Receptors in Leukocytes.

The word chemokine is a combination of the words chemotactic and cytokine, in other words cytokines that promote chemotaxis. Hence, the term chemokine receptor refers largely to the ability to regulate chemoattraction. However, these receptors can modulate additional leukocyte functions, as exemplified by the case of CCR7 which, apart from chemotaxis, regulates survival, migratory speed, endocytosis, differentiation and cytoarchitecture.

Complications in CO2 Laser Transoral Microsurgery for Larynx Carcinomas.

Introduction Transoral laser microsurgery (TLM) has established itself as an effective option in the management of malignant tumors of the glottis, supraglottis, and hypopharynx. Nonetheless, TLM is not a harmless technique. Complications such as bleeding, dyspnea, or ignition of the air may appear in this type of surgery.

Plasma membrane-associated superstructure: Have we overlooked a new type of organelle in eukaryotic cells?

A variety of intriguing plasma membrane-associated regions, including focal adhesions, adherens junctions, tight junctions, immunological synapses, neuromuscular junctions and the primary cilia, among many others, have been described in eukaryotic cells. Emphasizing their importance, alteration in their molecular structures induces or correlates with different pathologies. These regions display surface proteins connected to intracellular molecules, including cytoskeletal component, which maintain their cytoarchitecture, and signalling proteins, which regulate their organization and functions.

CXCL12 Regulates through JAK1 and JAK2 Formation of Productive Immunological Synapses.

The adaptive immune response requires interaction between T cells and APC to form a specialized structure termed the immune synapse (IS). Although the TCR is essential for IS organization, other factors such as chemokines participate in this process. In this study, we show that the chemokine CXCL12-mediated signaling contributes to correct IS organization and therefore influences T cell activation.

A novel MEK-ERK-AMPK signaling axis controls chemokine receptor CCR7-dependent survival in human mature dendritic cells.

Chemokine receptor CCR7 directs mature dendritic cells (mDCs) to secondary lymph nodes where these cells regulate the activation of T cells. CCR7 also promotes survival in mDCs, which is believed to take place largely through Akt-dependent signaling mechanisms. We have analyzed the involvement of the AMP-dependent kinase (AMPK) in the control of CCR7-dependent survival.

Detecting apoptosis of leukocytes in mouse lymph nodes.

Although there are multiple methods for analyzing apoptosis in cultured cells, methodologies for analyzing apoptosis in vivo are sparse. In this protocol, we describe how to detect apoptosis of leukocytes in mouse lymph nodes (LNs) via the detection of apoptotic caspases. We have previously used this protocol to study factors that modulate dendritic cell (DC) survival in LNs; however, it can also be used to analyze other leukocytes that migrate to the LNs.

Antigen presentation by dendritic cells in rheumatoid arthritis.

Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease that affects largely synovial joints. It has been postulated that activated autoreactive CD4 T cells play a key role in triggering and/or maintaining the chronic inflammatory process in RA. Dendritic cells (DCs) are antigen-presenting cells that activate cognate clonal CD4 T cells in the lymph nodes.

Aryl hydrocarbon receptor contributes to the MEK/ERK-dependent maintenance of the immature state of human dendritic cells.

Dendritic cells (DCs) promote tolerance or immunity depending on their maturation state, which is enhanced or accelerated upon MEK-ERK signaling pathway inhibition. We have determined the contribution of MEK-ERK activation to the profile of gene expression of human immature monocyte-derived dendritic cells (MDDCs) and peripheral blood myeloid DCs. ERK inhibition altered the expression of genes that mediate Chemokine (C-C motif) ligand 19 (CCL19)-directed migration (CCR7) and low-density lipoprotein (LDL) binding (CD36, SCARB1, OLR1, CXCL16) by immature DCs.

CD69 modulates sphingosine-1-phosphate-induced migration of skin dendritic cells.

In this study, we have investigated the role of CD69, an early inducible leukocyte activation receptor, in murine dendritic cell (DC) differentiation, maturation, and migration. Skin DCs and DC subsets present in mouse lymphoid organs express CD69 in response to maturation stimuli. Using a contact sensitization model, we show that skin DCs migrated more efficiently to draining lymph nodes (LNs) in the absence of CD69.

The neuronal protein Kidins220/ARMS associates with ICAM-3 and other uropod components and regulates T-cell motility.

Kinase D interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), is a protein that is mainly expressed in brain and neural cells where its function is only starting to be characterized. Here, we show that Kidins220/ARMS is also expressed in T lymphocytes where it is highly concentrated at the uropod of polarized T cells. In this cellular model, Kidins220/ARMS colocalizes with typical uropod T-cell molecules and coimmunoprecipitates with ICAM-3.

What is an immunological synapse?

Immunological synapses (IS) are emerging as highly organized 3D structures -formed by surface and cytoplasmic signalling and cytoskeletal molecules - that assemble at the zone of contact between a T cell and an antigen presenting cell (APC). The IS control functions that allow APC and T cells modulate the immune response.

CCR7-dependent stimulation of survival in dendritic cells involves inhibition of GSK3beta.

Chemokine receptor CCR7 regulates chemotaxis and survival in mature dendritic cells (DCs). We studied the role of glycogen synthase kinase-3beta (GSK3beta) in the regulation of CCR7-dependent survival. We show that GSK3beta behaves as a proapoptotic regulator in cultured monocyte-derived human DCs and murine splenic DCs in vitro, and in lymph node DCs in vivo.