Contents I. II. III. IV. V. VI. VII. VIII. IX.
Cytoskeletal microtubules (
To obtain the comprehensive transcriptome profile of human citrulline‐specific B cells from patients with rheumatoid arthritis (
Citrulline‐ and hemagglutinin‐specific B cells were sorted by flow cytometry using peptide–streptavidin conjugates from the peripheral blood of
Citrulline‐specific B cells, in comparison to citrulline‐negative B cells, from patients with
To the best of our knowledge, this is the first study to document the whole transcriptome profile of autoreactive B cells in any autoimmune disease. These data identify several genes and pathways that may be targeted by repurposing several
- Award ID(s):
- 1705464
- NSF-PAR ID:
- 10460996
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Arthritis & Rheumatology
- Volume:
- 71
- Issue:
- 4
- ISSN:
- 2326-5191
- Page Range / eLocation ID:
- p. 529-541
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Summary Introduction MT arrays in plant cells γ‐Tubulin and MT nucleation MT nucleation sites or flexible MTOCs in plant cells MT‐dependent MT nucleation Generating new MTs for spindle assembly Generation of MTs for phragmoplast expansion during cytokinesis MT generation for the cortical MT array MT nucleation: looking forward Acknowledgements References Summary MT s) have a multitude of functions including intracellular distribution of molecules and organelles, cell morphogenesis, as well as segregation of the genetic material and separation of the cytoplasm during cell division among eukaryotic organisms. In response to internal and external cues, eukaryotic cells remodel theirMT network in a regulated manner in order to assemble physiologically important arrays for cell growth, cell proliferation, or for cells to cope with biotic or abiotic stresses. Nucleation of newMT s is a critical step forMT remodeling. Although many key factors contributing toMT nucleation and organization are well conserved in different kingdoms, the centrosome, representing the most prominent microtubule organizing centers (MTOC s), disappeared during plant evolution as angiosperms lack the structure. Instead, flexibleMTOC s may emerge on the plasma membrane, the nuclear envelope, and even organelles depending on types of cells and organisms and/or physiological conditions.MT ‐dependentMT nucleation is particularly noticeable in plant cells because it accounts for the primary source ofMT generation for assembling spindle, phragmoplast, and cortical arrays when the γ‐tubulin ring complex is anchored and activated by the augmin complex. It is intriguing what proteins are associated with plant‐specificMTOC s and how plant cells activate or inactivateMT nucleation activities in spatiotemporally regulated manners. -
more » « less
Summary Signalling events downstream the B‐cell receptor (
BCR ) are central for the survival and progression of chronic lymphocytic leukaemia (CLL ) cells. Focal adhesion kinase (FAK ), regulated through calpain, interacts with molecules ofBCR signalling, cytoskeletal modelling and disease progression, such as Src/Lyn, cortactin andHS1 . Hypothesizing thatFAK might play a key role inCLL pathogenesis, we observed a down‐modulation ofFAK whole form, associated withFAK cleavage due to calpain activity uponBCR stimulation. Patients, whose cells were able to release Ca++afterBCR stimulation, had less amount of full‐lengthFAK , which translated into a higher presence of cleaved/activated form of the protein phosphorylated atY397 , these features being mostly shown by immunoglobulin heavy chain (IGHV )‐unmutated poor‐prognosis patients. Moreover, we found that cortactin andHS1 proteins were overexpressed in those cells, suggesting a possible interplay withFAK . Treatment with theFAK inhibitor Defactinib was able to induce apoptosis inCLL cells. In conclusion, the malignant phenotype in unfavourable‐prognosis patients seems to be encouraged by the overexpression of cortactin andHS1 , that, together withFAK , may be involved in a druggable pathogenetic pathway inCLL . -
more » « less
Summary Phagocytosis, macropinocytosis and antigen presentation by dendritic cells (
DC ) requires reorganization of the actin cytoskeleton. Drebrin (Dbn1) is an actin binding and stabilizing protein with roles in endocytosis, formation of dendrite spines in neurons and coordinating cell–cell synapses in immune cells. However, its role inDC phagocytosis and antigen presentation is unknown. These studies now report that silencing of Dbn1 inDC resulted in restrained cell surface display of receptors, most notablyMHC class I andII and co‐stimulatory molecules. This, as expected, resulted in impaired antigen‐specific T‐cell activation and proliferation. Studies additionally revealed that knockdown of Dbn1 inDC impaired macropinocytosis and phagocytosis. However, there was a concomitant increase in fluid‐phase uptake, suggesting that Dbn1 is responsible for the differential control of macropinocytosis versus micropinocytosis activities. Taken together, these findings now reveal that Dbn1 plays a major role in coordinating the actin cytoskeletal activities responsible for antigen presentation inDC . -
more » « less
Summary B‐cell responses are dynamic processes that depend on multiple types of interactions. Rare antigen‐specific B cells must encounter antigen and specialized systems are needed—unique to each lymphoid tissue type—to ensure this happens efficiently. Lymphoid tissue barrier cells act to ensure that pathogens, while being permitted entry for B‐cell recognition, are blocked from replication or dissemination. T follicular helper (Tfh) cells often need to be primed by dendritic cells before supporting B‐cell responses. For most responses, antigen‐specific helper T cells and B cells need to interact, first to initiate clonal expansion and the plasmablast response, and later to support the germinal center (
GC ) response. Newly formed plasma cells need to travel to supportive niches.GC B cells must become confined to the follicle center, organize into dark and light zones, and interact with Tfh cells. Memory B cells need to be positioned for rapid responses following reinfection. Each of these events requires the actions of multiple G‐protein coupled receptors (GPCR s) and their ligands, including chemokines and lipid mediators. This review will focus on the guidance cue code underlying B‐cell immunity, with an emphasis on findings from our laboratory and on newer advances in related areas. We will discuss our recent identification of geranylgeranyl‐glutathione as a ligand for P2RY8. Our goal is to provide the reader with a focused knowledge about theGPCR s guiding B‐cell responses and how they might be therapeutic targets, while also providing examples of how multiple types ofGPCR s can cooperate or act iteratively to control cell behavior. -
more » « less
Summary Here we report the expression of programmed cell death ligand 1/2 (
PD ‐L1/L2) in breast and colon cancer stem cells (CSC s). The stemness of these cells was confirmed by their surface markers. Using flow cytometry analysis we demonstrated thatPD ‐L1 expression was higher inCSC s of both cancers compared to non‐stem like cancer cells. Consistent with this, detection of cellularPD ‐L1 proteins by western blot assay also showed increasedPD ‐L1 protein inCSC s. In contrast, only trace amounts ofPD ‐L2 were detected inCSC s of both cancers. Our results suggest that breast and colon cancers may be sensitive toPD 1/PD ‐L1 immunotherapy and thus warrant further investigations ofCSC targetedPD 1/PD ‐L1 therapy.
