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Gareth W Jones, David G Hill, Simon A Jones
Tertiary lymphoid organs (TLOs) are frequently observed in tissues affected by non-resolving inflammation as a result of infection, autoimmunity, cancer, and allograft rejection. These highly ordered structures resemble the cellular composition of lymphoid follicles typically associated with the spleen and lymph node compartments. Although TLOs within tissues show varying degrees of organization, they frequently display evidence of segregated T and B cell zones, follicular dendritic cell networks, a supporting stromal reticulum, and high endothelial venules...
2016: Frontiers in Immunology
Zhongle Liu, Gary P Moran, Derek J Sullivan, Donna M MacCallum, Lawrence C Myers
Filamentous growth is a hallmark of C. albicans pathogenicity compared to less-virulent ascomycetes. A multitude of transcription factors regulate filamentous growth in response to specific environmental cues. Our work, however, suggests the evolutionary history of C. albicans that resulted in its filamentous growth plasticity may be tied to a change in the general transcription machinery rather than transcription factors and their specific targets. A key genomic difference between C. albicans and its less-virulent relatives, including its closest relative C...
October 2016: PLoS Genetics
Aliyah M Weinstein, Walter J Storkus
Peripheral node addressin (PNAd) marks high endothelial venules (HEV), which are crucial for the recruitment of lymphocytes into lymphoid organs in non-mucosal tissue sites. PNAd is a sulfated and fucosylated glycoprotein recognized by the prototypic monoclonal antibody, MECA-79. PNAd is the ligand for L-selectin, which is expressed on the surface of naive and central memory T cells, where it mediates leukocyte rolling on vascular endothelial surfaces. Although PNAd was first identified in the HEV of peripheral lymph nodes, recent work suggests a critical role for PNAd in the context of chronic inflammatory diseases, where it can be used as a marker for the formation of tertiary lymphoid organs (TLOs)...
2016: Frontiers in Immunology
Jan Kranich, Nike Julia Krautler
Follicular dendritic cells (FDCs) are stromal cells residing in primary follicles and in germinal centers of secondary and tertiary lymphoid organs (SLOs and TLOs). There, they play a crucial role in B-cell activation and affinity maturation of antibodies. FDCs have the unique capacity to bind and retain native antigen in B-cell follicles for long periods of time. Therefore, FDCs shape the B-cell antigenome (the sum of all B-cell antigens) in SLOs and TLOs. In this review, we discuss recent findings that explain how this stromal cell type can arise in almost any tissue during TLO formation and, furthermore, focus on the mechanisms of antigen capture and retention involved in the generation of long-lasting antigen depots displayed on FDCs...
2016: Frontiers in Immunology
Verónica Freire-Benéitez, Sarah Gourlay, Judith Berman, Alessia Buscaino
DNA repeats, found at the ribosomal DNA locus, telomeres and subtelomeric regions, are unstable sites of eukaryotic genomes. A fine balance between genetic variability and genomic stability tunes plasticity of these chromosomal regions. This tuning mechanism is particularly important for organisms such as microbial pathogens that utilise genome plasticity as a strategy for adaptation. For the first time, we analyse mechanisms promoting genome stability at the rDNA locus and subtelomeric regions in the most common human fungal pathogen: Candida albicans In this organism, the histone deacetylase Sir2, the master regulator of heterochromatin, has acquired novel functions in regulating genome stability...
July 1, 2016: Nucleic Acids Research
Xiaoguang Xu, Yong Han, Qiang Wang, Ming Cai, Yeyong Qian, Xinying Wang, Haiyan Huang, Liang Xu, Li Xiao, Bingyi Shi
PURPOSE: Tertiary lymphoid organs (TLOs) have been described within organ allografts, but whether they promote destructive or beneficial alloimmune responses remains controversial. This study aimed to characterize TLO distribution in human chronically rejected renal allografts and to explore their functions. METHODS: A total of 29 explanted chronically rejected and 12 acutely rejected renal allografts were analyzed by immunohistochemistry. The distribution of TLOs, T cells, follicular dendritic cells, B cells, and follicular regulatory T (Tfr) cells, as well as Ki67, peripheral lymph node addressin (PNAd), podoplanin, AID, IL-17, IL-21, IL-10, and C4d expression were detected by immunohistochemistry...
2016: Immunological Investigations
Meredith Newman, Catherine Minns Lowe, Karen Barker
OBJECTIVE: To systematically review the evidence of effectiveness of spinal orthoses for adults with vertebral osteoporosis. DATA SOURCES: We conducted a systematic literature search using the databases of PubMed, MEDLINE, EMBASE, AMED, CINAHL, PEDro, and the Cochrane Library from January 1995 to October 2014. STUDY SELECTION: Two reviewers evaluated eligibility. Randomized controlled trials (RCTs), pilot RCTs, and prospective nonrandomized controlled studies of spinal orthoses for people with vertebral osteoporosis or osteopenia with and without osteoporotic vertebral fracture (OVF) that examined outcomes related to fracture consolidation, pain, strength, posture, balance, physical function, quality of life, and complications were eligible...
June 2016: Archives of Physical Medicine and Rehabilitation
Francesca Barone, Saba Nayar, Joana Campos, Thomas Cloake, David R Withers, Kai-Michael Toellner, Yang Zhang, Lynette Fouser, Benjamin Fisher, Simon Bowman, Javier Rangel-Moreno, Maria de la Luz Garcia-Hernandez, Troy D Randall, Davide Lucchesi, Michele Bombardieri, Costantino Pitzalis, Sanjiv A Luther, Christopher D Buckley
The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs...
September 1, 2015: Proceedings of the National Academy of Sciences of the United States of America
Lucas Onder, Burkhard Ludewig
Atherosclerosis is a lipid-storage disease of arteries that is exacerbated by chronic inflammatory processes. In this issue of Immunity, Hu et al. (2015) demonstrate that T cell responses in atherosclerotic lesions are controlled in tertiary lymphoid organs in the arterial wall.
June 16, 2015: Immunity
Matthew Z Anderson, Lauren J Wigen, Laura S Burrack, Judith Berman
Subtelomeric regions of the genome are notable for high rates of sequence evolution and rapid gene turnover. Evidence of subtelomeric evolution has relied heavily on comparisons of historical evolutionary patterns to infer trends and frequencies of these events. Here, we describe evolution of the subtelomeric TLO gene family in Candida albicans during laboratory passaging for over 4000 generations. C. albicans is a commensal and opportunistic pathogen of humans and the TLO gene family encodes a subunit of the Mediator complex that regulates transcription and affects a range of virulence factors...
July 2015: Genetics
Beven P Livingston, T Richard Nichols
Nerve injury in the hindlimb of the cat results in locomotor changes, yet these findings have not been explored in a more multifunctional forelimb. Kinematics and muscle activity of the shoulder and elbow during level and upslope locomotion following reinnervation of the feline long head of the triceps brachii (TLo) were evaluated (1) during paralysis [none to minimum motor activity (short-term effects)] and (2) after the motor function was recovered but the proprioceptive feedback was permanently disrupted (long-term effects)...
2014: Cells, Tissues, Organs
Beven P Livingston, T Richard Nichols
Full recovery of the forelimb kinematics during level and upslope walking following reinnervation of the biarticular elbow extensor suggests that the proprioceptive loss is compensated by other sensory sources or altered central drive, yet these findings have not been explored in downslope walking. Kinematics and muscle activity of the shoulder and elbow during downslope locomotion following reinnervation of the feline long head of the triceps brachii (TLo) and biceps brachii (Bi) were evaluated (1) during paralysis and (2) after the motor function was recovered but the proprioceptive feedback was permanently disrupted...
2014: Cells, Tissues, Organs
Mizuno Sakai, Junkichi Yokoyama, Masatugu Tashiro, Tooru Ishikawa
Seven patients with advanced lateral oropharyngeal cancer (T3N2bM0, or T4N2bM0) underwent transoral lateral oropharyngectomy (TLO) with reconstruction performed through set-back tongue flap and polyglycolic acid (PGA) sheet. TLO was performed following en bloc resection of tumors using endoscopy. To cover the resulting defect in the lateral oropharyngeal wall, the set-back tongue flap was moved posteriorly and laterally to the area of the tongue base and lateral pharyngeal wall. The tip of the set-back tongue flap was sutured to the lateral pharynx to reconstruct the elevated tongue base and altered anterior pillar...
July 2015: Acta Oto-laryngologica
Manon M H Huibers, Alison J Gareau, Aryan Vink, Rianne Kruit, Hannah Feringa, Johanna M T Beerthuijzen, Erica Siera-de Koning, Ton Peeters, Nicolaas de Jonge, Roel A de Weger, Timothy D G Lee
BACKGROUND: Cardiac allograft vasculopathy (CAV) is a multifactorial pathology limiting the survival of cardiac transplants. The etiology of CAV is unclear, but antibody-mediated and cellular-mediated responses have been implicated. We, and others, have observed ectopic lymphoid structures (ELS) surrounding epicardial coronary arteries with CAV. The potential contribution of these ELS to CAV has not been elucidated. METHODS: Epicardial coronary arteries were collected from 59 transplant patients at 2 centers and studied for ELS presence and composition using immunohistochemistry...
May 2015: Journal of Heart and Lung Transplantation
M Bonnan
Multiple sclerosis (MS) is characterized by an intrathecal synthesis of immunoglobulins synthesized by B-cell clones and by a brain infiltrate of clonal T-cells. The clonal maturation of these lymphocytes takes place in tertiary lymphoid organs (TLO) developed in the intrathecal compartment. TLO are acquired lymphoid organs able to develop in the vicinity of the inflammatory sites, where they mount a complete antigen-driven immune response. We here review TLO pathophysiology in animal models of MS and human MS...
January 2015: Revue Neurologique
John Haran, Hannah Boyle, Karsten Hokamp, Tim Yeomans, Zhongle Liu, Michael Church, Alastair B Fleming, Matthew Z Anderson, Judith Berman, Lawrence C Myers, Derek J Sullivan, Gary P Moran
The TLO genes are a family of telomere-associated ORFs in the fungal pathogens Candida albicans and C. dubliniensis that encode a subunit of the Mediator complex with homology to Med2. The more virulent pathogen C. albicans has 15 copies of the gene whereas the less pathogenic species C. dubliniensis has only two (CdTLO1 and CdTLO2). In this study we used C. dubliniensis as a model to investigate the role of TLO genes in regulating virulence and also to determine whether TLO paralogs have evolved to regulate distinct functions...
October 2014: PLoS Genetics
Matthew Z Anderson, Aleeza C Gerstein, Lauren Wigen, Joshua A Baller, Judith Berman
Cell-to-cell gene expression noise is thought to be an important mechanism for generating phenotypic diversity. Furthermore, telomeric regions are major sites for gene amplification, which is thought to drive genetic diversity. Here we found that individual subtelomeric TLO genes exhibit increased variation in transcript and protein levels at both the cell-to-cell level as well as at the population-level. The cell-to-cell variation, termed Telomere-Adjacent Gene Expression Noise (TAGEN) was largely intrinsic noise and was dependent upon genome position: noise was reduced when a TLO gene was expressed at an ectopic internal locus and noise was elevated when a non-telomeric gene was expressed at a telomere-adjacent locus...
July 2014: PLoS Genetics
Chang Hwan Ryu, Junsun Ryu, Kwan Ho Cho, Sung Ho Moon, Tak Yun, Sang-Hyun Lee, Moon Kyung Choi, Weon Seo Park, Yuh-S Jung
OBJECTIVES: To identify the prognostic implications of human papillomavirus (HPV)-related cell cycle marker profiles in patients who have received a transoral lateral oropharyngectomy (TLO) as a primary treatment for tonsillar squamous cell carcinoma (TSCC). PATIENTS AND METHODS: Immunohistochemical profiles of HPV-related cell cycle markers, including p16, pRb, cyclin D1, p53, and the HPV DNA status of 42 consecutive TSCC patients who underwent TLO-based treatments were analyzed...
September 2014: Journal of Surgical Oncology
Theresa Hautz, Bettina G Zelger, Isam W Nasr, Gerhard S Mundinger, Rolf N Barth, Eduardo D Rodriguez, Gerald Brandacher, Annemarie Weissenbacher, Bernhard Zelger, Pedro Cavadas, Raimund Margreiter, W P Andrew Lee, Johann Pratschke, Fadi G Lakkis, Stefan Schneeberger
The mechanisms of skin rejection in vascularized composite allotransplantation (VCA) remain incompletely understood. The formation of tertiary lymphoid organs (TLO) in hand transplantation has been recently described. We assess this phenomenon in experimental and clinical VCA rejection. Skin biopsies of human (n = 187), nonhuman primate (n = 11), and rat (n = 15) VCAs were analyzed for presence of TLO. A comprehensive immunohistochemical assessment (characterization of the cell infiltrate, expression of adhesion molecules) including staining for peripheral node addressin (PNAd) was performed and correlated with rejection and time post-transplantation...
September 2014: Transplant International: Official Journal of the European Society for Organ Transplantation
Mickael Bonnan
Although partly disease-irrelevant, intrathecal immunoglobulins (Ig) synthesis is a typical feature of multiple sclerosis (MS) and is driven by the tertiary lymphoid organs (TLO). A long-known hallmark of this non-specific intrathecal synthesis is the MRZ pattern, an intrathecal synthesis of Ig against measles, rubella, and zoster viruses. This non-specific intrathecal synthesis could also be directed against a wide range of pathogens. However, it is highly problematic since brain TLO should not be able to drive the clonal expansion of lymphocytes against alien antigens that are thought to be absent in MS brain...
2014: Frontiers in Neurology
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