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Ectopic lymphoid follicles

Toshiaki Kogame, Ryosuke Yamashita, Masahiro Hirata, Tatsuki R Kataoka, Hisashi Kamido, Chiyuki Ueshima, Miho Matsui, Takashi Nomura, Kenji Kabashima
Lupus erythematosus profundus (LEP) is a variant of lupus erythematosus, involving the deep dermis and subcutaneous fat. LEP is characterized by the presence of lymphoid follicles (LF) and germinal centers (GC). However, it remains unknown whether these lymphoid structures correspond to the lymphoid tissues such as cutaneous tertiary lymphoid organs (TLO). Previously, we identified dynamically orchestrated cellular elements in murine contact dermatitis that resembled lymphoid structures, which we termed inducible skin-associated lymphoid tissues (iSALT)...
June 13, 2018: Journal of Dermatology
Josefine Radke, Randi Koll, Corinna Preuße, Debora Pehl, Kremena Todorova, Constanze Schönemann, Yves Allenbach, Eleonora Aronica, Marianne de Visser, Frank L Heppner, Joachim Weis, Soroush Doostkam, Thierry Maisonobe, Olivier Benveniste, Hans-Hilmar Goebel, Werner Stenzel
Objective: To study the B-cell content, organization, and existence of distinct B-cell subpopulations in relation to the expression of type 1 interferon signature related genes in dermatomyositis (DM). Methods: Evaluation of skeletal muscle biopsies from patients with adult DM (aDM) and juvenile DM (jDM) by histology, immunohistochemistry, electron microscopy, and quantitative reverse-transcription PCR. Results: We defined 3 aDM subgroups-classic (containing occasional B cells without clusters), B-cell-rich, and follicle-like aDM-further elucidating IM B-lymphocyte maturation and immunity...
May 2018: Neurology® Neuroimmunology & Neuroinflammation
Kalyna Jakibchuk, Sophia Ali, Julie Samantray
A 40-year-old woman with a history of Graves' disease status postorbital decompression for severe ophthalmopathy underwent total thyroidectomy by a high volume thyroid surgeon in July 2013 with a benign final pathology. Eight months later, she presented with a mass on the right anterior neck that showed minimal growth over time. Her thyroid stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels were consistently elevated and increasing. She underwent removal of the neck mass in September 2016...
January 23, 2018: BMJ Case Reports
Taylor Eddens, Waleed Elsegeiny, Maria de la Luz Garcia-Hernadez, Patricia Castillo, Giraldina Trevejo-Nunez, Katelin Serody, Brian T Campfield, Shabaana A Khader, Kong Chen, Javier Rangel-Moreno, Jay K Kolls
Inducible bronchus-associated lymphoid tissue (iBALT) is an ectopic lymphoid structure composed of highly organized T cell and B cell zones that forms in the lung in response to infectious or inflammatory stimuli. Here, we develop a model for fungal-mediated iBALT formation, using infection with Pneumocystis that induces development of pulmonary lymphoid follicles. Pneumocystis-dependent iBALT structure formation and organization required CXCL13 signaling. Cxcl13 expression was regulated by interleukin (IL)-17 family members, as Il17ra-/- , Il17rb-/- , and Il17rc-/- mice failed to develop iBALT...
March 28, 2017: Cell Reports
C S Horjus Talabur Horje, C Smids, J W R Meijer, M J Groenen, M K Rijnders, E G van Lochem, P J Wahab
Naive and central memory T lymphocytes (TN and TCM ) can infiltrate the inflamed gut mucosa in inflammatory bowel disease (IBD) patients. Homing of these subsets to the gut might be explained by ectopic formation of tertiary lymphoid organs (TLOs), containing high endothelial venules (HEVs). We aimed to evaluate the presence of HEVs and TLOs in inflamed intestinal mucosa of newly diagnosed, untreated IBD patients in relation to the presence of TN and TCM lymphocytes. IBD patients (n = 39) and healthy controls (n = 8) were included prospectively...
April 2017: Clinical and Experimental Immunology
Feifeng Jing, Eun Young Choi
Tertiary lymphoid structures (TLS) are ectopic lymphoid tissues involved in chronic inflammation, autoimmune diseases, transplant rejection and cancer. They exhibit almost all the characteristics of secondary lymphoid organs (SLO), which are associated with adaptive immune responses; as such, they contain organized B-cell follicles with germinal centers, distinct areas containing T cells and dendritic cells, high endothelial venules, and lymphatics. In this review, we briefly describe the formation of SLO, and describe the cellular subsets and molecular cues involved in the formation and maintenance of TLS...
October 2016: Immune Network
Atsushi Abe, Tatsuya Manabe, Nobuyoshi Takizawa, Takashi Ueki, Daisuke Yamada, Kinuko Nagayoshi, Yoshihiko Sadakari, Hayato Fujita, Shuntaro Nagai, Hidetaka Yamamoto, Yoshinao Oda, Masafumi Nakamura
Sclerosing mesenteritis (SM) is a rare inflammatory and fibrosing disease primarily involving the small-bowel mesentery. Recently, SM was reported to be closely related to IgG4-related disease (IgG4-RD). This report describes a patient with SM associated with IgG4-RD. A 77-year-old woman with a history of surgery for ectopic pregnancy and wound dehiscence presented with intestinal obstruction. Abdominal enhanced computed tomography (CT) revealed an enhanced, radially shaped, oval mass, 3 cm in diameter, with an unclear rim in the mesentery of the distal ileum, which may have involved the distal ileum...
December 2016: Surgical Case Reports
Kristina J H Kleinwort, Barbara Amann, Stefanie M Hauck, Regina Feederle, Walter Sekundo, Cornelia A Deeg
PURPOSE: Recently, formation of tertiary lymphoid structures was demonstrated and further characterized in the R161H mouse model of spontaneous autoimmune uveitis. In the horse model of spontaneous recurrent uveitis, intraocular lymphoid follicle formation is highly characteristic, and found in all stages and scores of disease, but in depth analyses of immunologic features of these structures are lacking to date. METHODS: Paraffin-embedded eye sections of cases with equine spontaneous recurrent uveitis (ERU) were characterized with immunohistochemistry to gain insight into the distribution, localization, and signaling of immune cells in intraocular tertiary lymphoid tissues...
August 1, 2016: Investigative Ophthalmology & Visual Science
Barbara Serafini, Barbara Rosicarelli, Caterina Veroni, Ling Zhou, Camilla Reali, Francesca Aloisi
Ectopic B-cell follicle-like structures (ELS) are found in the meninges of patients with secondary progressive multiple sclerosis (SPMS). Because cells expressing the transcriptional regulator retinoic acid receptor-related orphan receptor-γt (RORγt) and producing interleukin 17 (IL17), e.g. T helper 17 cells and lymphoid tissue inducer (LTi) cells, have been implicated in the formation of ELS, we studied RORγt and IL17 expression in brain tissue from patients with SPMS an assessed their relationships to immune infiltrates and meningeal ELS...
September 2016: Journal of Neuropathology and Experimental Neurology
Marc Clement, Adrien Galy, Patrick Bruneval, Marion Morvan, Fabien Hyafil, Khadija Benali, Nicoletta Pasi, Lydia Deschamps, Quentin Pellenc, Thomas Papo, Antonino Nicoletti, Karim Sacre
OBJECTIVE: The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients. METHODS: Hematoxylin and eosin-stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry...
2016: Frontiers in Immunology
Ming Zeng, Anthony J Smith, Liang Shang, Stephen W Wietgrefe, James E Voss, John V Carlis, Qingsheng Li, Michael Piatak, Jeffrey D Lifson, R Paul Johnson, Ashley T Haase
Live attenuated vaccines such as SIV with a deleted nef gene have provided the most robust protection against subsequent vaginal challenge with wild-type (WT) SIV in the SIV-rhesus macaque model of HIV-1 transmission to women. Hence, identifying correlates of this protection could enable design of an effective HIV-1 vaccine. One such prechallenge correlate of protection from vaginal challenge has recently been identified as a system with three components: 1) IgG Abs reacting with the viral envelope glycoprotein trimeric gp41; 2) produced by plasma cells in the submucosa and ectopic tertiary lymphoid follicles in the ectocervix and vagina; and 3) concentrated on the path of virus entry by the neonatal FcR in the overlying epithelium...
March 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Carlos Alfaro, Jose I Echeveste, Maria E Rodriguez-Ruiz, Jose L Solorzano, Jose L Perez-Gracia, Miguel A Idoate, Jose M Lopez-Picazo, Alfonso R Sanchez-Paulete, Sara Labiano, Ana Rouzaut, Carmen Oñate, Angela Aznar, Maria D Lozano, Ignacio Melero
CD137 (4-1BB) is a surface protein initially discovered to mark activated T lymphocytes. However, its broader expression pattern also encompasses activated NK cells, B cells and myeloid cells, including mature dendritic cells. In this study, we have immunostained for CD137 on paraffin-embedded lymphoid tissues including tonsils, lymph nodes, ectopic tertiary lymphoid tissue in Hashimoto thyroiditis and cancer. Surprisingly, immunostaining mainly decorated intrafollicular lymphocytes in the tissues analyzed, with only scattered staining in interfollicular areas...
December 2015: Oncoimmunology
Gareth W Jones, Simon A Jones
Lymphoid neogenesis is traditionally viewed as a pre-programmed process that promotes the formation of lymphoid organs during development. Here, the spatial organization of T and B cells in lymph nodes and spleen into discrete structures regulates antigen-specific responses and adaptive immunity following immune challenge. However, lymphoid neogenesis is also triggered by chronic or persistent inflammation. Here, ectopic (or tertiary) lymphoid organs frequently develop in inflamed tissues as a response to infection, auto-immunity, transplantation, cancer or environmental irritants...
February 2016: Immunology
Lu Wang, Wei-Ping Zhang, Li Yao, Wei Zhang, Jin Zhu, Wei-Chen Zhang, Yue-Hua Zhang, Zhe Wang, Qing-Guo Yan, Ying Guo, Lin-Ni Fan, Yi-Xiong Liu, Gao-Sheng Huang
Ectopic lymphoid follicle infiltration is a key event in Hashimoto thyroiditis (HT). Positive regulatory domain zinc finger protein 1 (PRDM1), which is induced by antigen stimulation, can regulate all lymphocyte lineages. Several groups independently demonstrated that human parvovirus B19 (PVB19) is closely associated with HT. Hence, we determined whether PRDM1 is expressed in HT thyroid tissue and whether there is any correlation between PRDM1 expression and PVB19 in the pathogenesis of HT. We detected PRDM1 expression in HT (n = 86), normal thyroid tissue (n = 30), and nontoxic nodular goiter (n = 20) samples using immunohistochemistry...
December 2015: Human Pathology
Julianne K Hatfield, Melissa A Brown
Innate lymphoid cells are immune cells that reside in tissues that interface with the external environment and contribute to the first line defense against pathogens. However, they also have roles in promoting chronic inflammation. Here we demonstrate that group 3 ILCs, (ILC3s - CD45+Lin-IL-7Rα+RORγt+), are normal residents of the meninges and exhibit disease-induced accumulation and activation in EAE. In addition to production of the pro-inflammatory cytokines IL-17 and GM-CSF, ILC3s constitutively express CD30L and OX40L, molecules required for memory T cell survival...
October 2015: Cellular Immunology
Juan D Cañete, Raquel Celis, Nataliya Yeremenko, Raimon Sanmartí, Leonie van Duivenvoorde, Julio Ramírez, Iris Blijdorp, Carmen M García-Herrero, José L Pablos, Dominique L Baeten
INTRODUCTION: The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. METHODS: Synovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively...
2015: Arthritis Research & Therapy
Ekaterina Klimatcheva, Tracy Pandina, Christine Reilly, Sebold Torno, Holm Bussler, Maria Scrivens, Alan Jonason, Crystal Mallow, Michael Doherty, Mark Paris, Ernest S Smith, Maurice Zauderer
BACKGROUND: Homeostatic B Cell-Attracting chemokine 1 (BCA-1) otherwise known as CXCL13 is constitutively expressed in secondary lymphoid organs by follicular dendritic cells (FDC) and macrophages. It is the only known ligand for the CXCR5 receptor, which is expressed on mature B cells, follicular helper T cells (Tfh), Th17 cells and regulatory T (Treg) cells. Aberrant expression of CXCL13 within ectopic germinal centers has been linked to the development of autoimmune disorders (e.g...
2015: BMC Immunology
Josefine Radke, Debora Pehl, Eleonora Aronica, Dieneke Schonenberg-Meinema, Udo Schneider, Frank L Heppner, Marianne de Visser, Hans H Goebel, Werner Stenzel
OBJECTIVE: To investigate the clinical and morphologic spectrum of early adult-onset dermatomyositis (DM), an inflammatory disease that affects small vessels of the muscle and the skin. METHODS: Histologic evaluation of frozen muscle samples was employed to visualize the cellular organization of ectopic lymphoid structures in muscle biopsies obtained from 2 patients diagnosed with DM. Clinical presentation and morphologic features, as well as treatment and follow-up, were assessed and documented...
August 2014: Neurology® Neuroimmunology & Neuroinflammation
Qingsheng Li, Ming Zeng, Lijie Duan, James E Voss, Anthony J Smith, Stefan Pambuccian, Liang Shang, Stephen Wietgrefe, Peter J Southern, Cavan S Reilly, Pamela J Skinner, Mary L Zupancic, John V Carlis, Michael Piatak, Diane Waterman, R Keith Reeves, Katherine Masek-Hammerman, Cynthia A Derdeyn, Michael D Alpert, David T Evans, Heinz Kohler, Sybille Müller, James Robinson, Jeffrey D Lifson, Dennis R Burton, R Paul Johnson, Ashley T Haase
We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239Δnef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG Abs reactive with viral envelope glycoprotein gp41 trimers, and these Abs are concentrated on the path of virus entry by the neonatal FcR in cervical reserve epithelium and in vaginal epithelium...
September 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Jodi L Karnell, Tamer I Mahmoud, Ronald Herbst, Rachel Ettinger
Ectopic follicles are non-encapsulated organized lymphoid structures that form at sites of inflammation and presumably contribute to the activation and differentiation of cells with autoreactive potential within target tissues. As such, directed targeting of ectopic follicles in settings of autoimmunity may provide a means to specifically inhibit the activation of autoreactive cells without impairing protective immune responses ongoing in peripheral lymphoid tissues. NOD·H2h4 mice are a non-diabetic strain of NOD mice which develop a Sjögren's syndrome-like disease which includes the formation of ectopic follicles in the salivary gland and characteristic Sjögren's autoantibodies...
December 2014: Molecular Immunology
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