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Bcl6 and dendritic cells

Siyu Deng, Qianwen Hu, Heng Zhang, Fang Yang, Cheng Peng, Chuanxin Huang
Programmed cell-death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway blockade is a promising therapy for the treatment of advanced cancers including B-cell lymphoma. The clinical response to PD-1/PD-L1 immunotherapy correlates with PD-L1 levels on tumor cells and other cells in the tumor microenvironment. Hence, it is important to understand the molecular mechanisms that regulate PD-L1 expression. Here, we report that histone deacetylase 3 (HDAC3) is a crucial repressor of PD-L1 transcription in B-cell lymphoma...
March 1, 2019: Molecular Cancer Therapeutics
Chan Johng Kim, Choong-Gu Lee, Ju-Yang Jung, Ambarnil Ghosh, Syed Nurul Hasan, Sung-Min Hwang, Hyeji Kang, Changhon Lee, Gi-Cheon Kim, Dipayan Rudra, Chang-Hee Suh, Sin-Hyeog Im
Single-nucleotide polymorphisms in ETS1 are associated with systemic lupus erythematosus (SLE). Ets1-/- mice develop SLE-like symptoms, suggesting that dysregulation of this transcription factor is important to the onset or progression of SLE. We used conditional deletion approaches to examine the impact of Ets1 expression in different immune cell types. Ets1 deletion on CD4+ T cells, but not B cells or dendritic cells, resulted in the SLE autoimmunity, and this was associated with the spontaneous expansion of T follicular helper type 2 (Tfh2) cells...
December 18, 2018: Immunity
Qingshun Lin, Mareki Ohtsuji, Hirofumi Amano, Hiromichi Tsurui, Norihiro Tada, Ryota Sato, Hidehiro Fukuyama, Hiroyuki Nishimura, J Sjef Verbeek, Sachiko Hirose
C57BL/6 (B6).FcγRIIb-/- Yaa mice spontaneously develop lethal lupus nephritis. To define the cell type-specific role of FcγRIIb in Yaa -associated lupus, we established B cell- (CD19Cre Yaa ), myeloid cell- (C/EBPαCre Yaa ), and dendritic cell- (DC) (CD11cCre Yaa ) specific FcγRIIb-deficient B6. Yaa mouse strains. CD19Cre Yaa mice developed milder lupus than B6.FcγRIIb-/- Yaa mice, indicating that FcγRIIb deficiency on B cells is not sufficient for the development of severe disease. Surprisingly, C/EBPαCre Yaa mice also showed autoantibody production and mild lupus similar to that in CD19Cre Yaa mice, whereas CD11cCre Yaa mice stayed disease free...
October 29, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Joji Shimono, Hiroaki Miyoshi, Fumiko Arakawa, Hideyuki Abe, Takuto Miyagishima, Jun Akiba, Takanori Teshima, Koichi Ohshima
Langerhans cell sarcoma (LCS) is a very rare histiocytic and dendritic cell neoplasm originating from Langerhans cells. There are case reports of histiocytic and dendritic cell neoplasms synchronously or sequentially observed in patients with malignant lymphoma. We present a case in which LCS and follicular lymphoma (FL) grade 3a were observed within the same lymph node. A 66-year-old male visited our hospital with a general malaise. Pleural effusion and systemic lymph adenopathy were detected. Biopsy of an inguinal lymph node was performed...
November 2018: Pathology International
Soochan Kim, Sinsuk Han, Taehyun Kim, Jeehoon Nam, Yong-Sun Kim, Eun-Kyoung Choi, Mi-Yeon Kim
We previously reported that mice intracerebrally inoculated with the mouse-adapted scrapie strain ME7 have markedly diminished T zones in the spleen due to the decreased expression of CCL19 and CCL21. In addition, follicular dendritic cell networks in germinal centers were larger in ME7-infected spleens compared to uninfected spleens. As an extension of that study, we set out to determine how ME7 infection affects spleen structure and follicular helper T (Tfh) cell responses in mice. For this study, mice were intraperitoneally inoculated with brain homogenate of the ME7 inoculum and spleens were analyzed 50, 130, and 200 days after inoculation and compared with those from uninfected mice...
March 4, 2018: Prion
Tanushri Mukherjee, Rajat Dutta, S Pramanik
Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T cell non-Hodgkin lymphoma with an aggressive fatal course and it has varied clinical presentation with an uncommon presentation when they present as soft tissue masses or when there is spill in the peripheral blood or there are composite lymphomas that are rare presentations. Common presentations include lymphadenopathy, fever and systemic symptoms, hemolytic anemias, skin rashes, and rheumatoid arthritis. The classical histopathology is absence of follicles in lymph nodes with presence of high endothelial venules and the tumor cells of small to medium-sized lymphocytes with pale cytoplasm mixed with reactive T cells...
March 2018: Indian Journal of Surgical Oncology
Kiryeong Kim, Tae Hoon Kim, Hye Jung Ihn, Jung Eun Kim, Je-Yong Choi, Hong-In Shin, Eui Kyun Park
Purpurogallin, a benzotropolone-containing natural compound, has been reported to exhibit numerous biological and pharmacological functions, such as antioxidant, anticancer, and anti-inflammatory effects. In this study, we enzymatically synthesized purpurogallin from pyrogallol and investigated its role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Purpurogallin attenuated the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts from bone marrow macrophages (BMMs) without causing cytotoxicity, and suppressed upregulation of osteoclast-specific markers, including TRAP (Acp5), cathepsin K (Ctsk), and dendritic cell-specific transmembrane protein (Dcstamp)...
February 17, 2018: International Journal of Molecular Sciences
K de Leur, M C Clahsen-van Groningen, T P P van den Bosch, G N de Graav, D A Hesselink, J N Samsom, C C Baan, K Boer
We hypothesize that T cells such as interleukin (IL)-21+ B cell lymphoma 6 (BCL6)+ T follicular helper cells can regulate B cell-mediated immunity within the allograft during acute T cell-mediated rejection; this process may feed chronic allograft rejection in the long term. To investigate this mechanism, we determined the presence and activation status of organized T and B cells in so-called ectopic lymphoid structures (ELSs) in different types of acute renal allograft rejection. Biopsies showing the following primary diagnosis were included: acute/active antibody-mediated rejection, C4d+ (a/aABMR), acute T cell-mediated rejection grade I (aTCMRI) and acute T cell-mediated rejection grade II (aTCMRII)...
May 2018: Clinical and Experimental Immunology
Chie Sakimura, Hiroaki Tanaka, Takahiro Okuno, Soichiro Hiramatsu, Kazuya Muguruma, Kosei Hirakawa, Hideki Wanibuchi, Masaichi Ohira
BACKGROUND: The role of tumor-infiltrating B cells in the tumor microenvironment is still unclear. Recent studies have reported that B cells and tertiary lymphoid structures (TLSs) that contain B cell follicles correlate with the favorable prognosis of cancer patients. The aim of this study was to investigate the association between tumor-infiltrating B cells and clinicopathological features in gastric cancer. METHODS: Tumor blocks were obtained from 226 patients with stage Ib to stage IV gastric cancer...
July 2017: Journal of Surgical Research
Lucia Pattarini, Coline Trichot, Sofia Bogiatzi, Maximilien Grandclaudon, Stephan Meller, Zela Keuylian, Melanie Durand, Elisabetta Volpe, Stefania Madonna, Andrea Cavani, Andrea Chiricozzi, Marco Romanelli, Toshiyuki Hori, Alain Hovnanian, Bernhard Homey, Vassili Soumelis
T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells...
May 1, 2017: Journal of Experimental Medicine
Satoru Yamasaki, Kanako Shimizu, Kohei Kometani, Maki Sakurai, Masami Kawamura, Shin-Ichiro Fujii
An induction of long-term cellular and humoral immunity is for the goal of vaccines, but the combination of antigens and adjuvant remain unclear. Here, we show, using a cellular vaccine carrying foreign protein antigen plus iNKT cell glycolipid antigen, designated as artificial adjuvant vector cells (aAVCs), that mature XCR1- DCs in situ elicit not only ordinal antigen-specific CD4+ T cells, but also CD4+ Tfh and germinal center, resulted in inducing long-term antibody production. As a mechanism for leading the long-term antibody production by aAVC, memory CD4+ Tfh cells but not iNKTfh cells played an important role in a Bcl6 dependent manner...
October 14, 2016: Scientific Reports
Michel Varrin-Doyer, Kara L Pekarek, Collin M Spencer, Claude C A Bernard, Raymond A Sobel, Bruce A C Cree, Ulf Schulze-Topphoff, Scott S Zamvil
OBJECTIVE: To evaluate the influence of oral laquinimod, a candidate multiple sclerosis (MS) treatment, on induction of T follicular helper cells, development of meningeal B cell aggregates, and clinical disease in a spontaneous B cell-dependent MS model. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by immunization with recombinant myelin oligodendrocyte glycoprotein (rMOG) protein. Spontaneous EAE was evaluated in C57BL/6 MOG p35-55-specific T cell receptor transgenic (2D2) × MOG-specific immunoglobulin (Ig)H-chain knock-in (IgH(MOG-ki) [Th]) mice...
October 2016: Neurology® Neuroimmunology & Neuroinflammation
Nobuhiko Ohnishi, Katsuyoshi Takata, Tomoko Miyata-Takata, Yasuharu Sato, Akira Tari, Yuka Gion, Mai Noujima-Harada, Kohei Taniguchi, Tetsuya Tabata, Keina Nagakita, Shizuma Omote, Hiroyuki Takahata, Masaya Iwamuro, Hiroyuki Okada, Yoshinobu Maeda, Hiroyuki Yanai, Tadashi Yoshino
Follicular lymphoma (FL) shows co-expression of B-cell lymphoma 2 (BCL2) and CD10, whereas downexpression of CD10 is occasionally experienced in gastrointestinal (GI) FL with unknown significance. Gastrointestinal FL is a rare variant of FL, and its similarity with mucosa-associated lymphoid tissue lymphoma was reported. We investigated the clinicopathological and genetic features of CD10 downexpressed (CD10(down) ) GI-FL. The diagnosis of CD10(down) FL was carried out with a combination of pathological and molecular analyses...
November 2016: Cancer Science
Daisuke Kurita, Hiroaki Miyoshi, Noriaki Yoshida, Yuya Sasaki, Seiichi Kato, Daisuke Niino, Yasuo Sugita, Yoshihiro Hatta, Masami Takei, Makoto Makishima, Koichi Ohshima
Lennert lymphoma (LeL) is a variant of peripheral T-cell lymphoma, not otherwise specified. Few clinicopathologic studies have investigated LeL, which is a rare disease. Here, we analyzed the clinicopathologic features of 26 patients with LeL to identify potential prognostic factors. Neoplastic cells positive for CD4, CD8, CD4/CD8, TIA-1, and granzyme B were observed in 21 (80.8%), 4 (15.4%), 1 (3.8%), 4 (15.3%), and 0 (0.0%) patients, respectively. Regarding follicular helper T-cell (TFH) markers, neoplastic cells positive for programmed cell death-1 (PD-1), CXCL13, CD10, and BCL6 were observed in 14 (53...
September 2016: American Journal of Surgical Pathology
Yu Kato, Ali Zaid, Gayle M Davey, Scott N Mueller, Stephen L Nutt, Dimitra Zotos, David M Tarlinton, Ken Shortman, Mireille H Lahoud, William R Heath, Irina Caminschi
Targeting Ags to dendritic cell (DC) surface receptors can induce a variety of responses depending on the DC type targeted, the receptor targeted, and the adjuvant used. Clec9A (DNGR-1), which is expressed by CD8(+) DCs, has been shown to bind F-actin exposed on damaged cells. Targeting Ag to this receptor in mice and nonhuman primates induces strong humoral immunity even in the absence of adjuvant, a process seen for a few select DC receptors. In contrast with other receptors, however, targeting Clec9A induces long-lived, affinity-matured Ab responses that are associated with efficient CD4(+) T cell responses shown to possess properties of follicular Th cells (TFH)...
August 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Dirk Baumjohann, K Mark Ansel
T follicular helper (Tfh) cells provide essential help to B cells for the generation of high-affinity antibodies. These mechanisms provide the basis for the success of modern vaccines, but dysregulated Tfh cell responses are also linked to autoimmune diseases. In addition to their established role in driving humoral immunity, Tfh cells are gaining attention for their role in other processes of the adaptive immune system. For example, Tfh cells may serve as transitional differentiation intermediates during effector and memory T-helper cell differentiation and as a reservoir of HIV-infected cells...
2015: Methods in Molecular Biology
Yanna Ding, John D Mountz, Hui-Chen Hsu
Follicular T helper (Tfh) cells are a critical population of CD4 T helper cells that are primarily localized in the germinal centers (GCs) to help B cell maturation and antibody production. Tfh cells can be identified in tissue sections based on the expression of a panel of classical Tfh surface makers, transcription marker(s), and effector-function cytokines, as well as by their unique anatomic proximity to other GC cells, including follicular dendritic cells (FDC) and GC B cells. Here, we describe an immunofluorescence staining method for visualization of GC Tfh cells in frozen spleen tissue sections of the autoimmune BXD2 mouse using a confocal imaging strategy...
2015: Methods in Molecular Biology
Mai Tatsuno, Akiko Miyagi Maeshima, Sung-Won Kim, Dai Maruyama, Hirokazu Taniguchi, Ken-ichi Miyamoto, Suguru Fukuhara, Yukio Kobayashi, Kensei Tobinai, Ryoji Kushima
We here report on two rare cases of intrafollicular classical Hodgkin lymphoma (CHL). Case 1 was a 34-year-old man who underwent left supraclavicular lymph node biopsy. Case 2 was a 28-year-old woman who underwent surgical resection of an anterior mediastinal mass. The histology and microenvironment of both specimens resembled those of nodular lymphocyte predominant Hodgkin lymphoma. Nodular architecture was observed, which comprised normal-appearing small lymphocytes and scattered lymphocyte predominant (LP)-like cells...
December 2014: Pathology International
Prokopios P Argyris, Ioannis G Koutlas, Sarah Cooley, Sophia L Yohe, Keta Bhakta, Rajaram Gopalakrishnan
Angioimmunoblastic T-cell lymphoma (AITL) is a rare neoplastic process constituting 15% to 20% of peripheral T-cell lymphomas. We report the clinicopathologic and molecular characteristics of an unusual intraoral manifestation of AITL. A 35-year-old white man with a history of AITL presented with a 2.5-cm, poorly circumscribed, erythematous, exophytic lesion occupying the free and attached buccal gingiva of the right maxillary lateral incisor and canine. Histopathologically, the tumor showed diffuse and intense polymorphic infiltration by small to medium-sized lymphocytes admixed with numerous eosinophils...
December 2014: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Yin- Ping Wong, Faridah Abdul-Rahman, Aamad Toha Samsudin, Noraidah Masir
Follicular lymphoma is characterised by the t(14;18)(q32;q21) chromosomal translocation causing BCL2 protein overexpression. A proportion of follicular lymphomas do not carry the t(14;18) translocation and lacked BCL2 protein expression. We describe a case of a BCL2 protein- and t(14;18)-negative follicular lymphoma that caused diagnostic difficulty. The usefulness of several immunomarkers including Ki67, CD79a and CD21 in aiding the diagnosis is discussed. The patient is a 51-year-old male who presented with gradually enlarging lymphadenopathy...
August 2014: Malaysian Journal of Pathology
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