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https://www.readbyqxmd.com/read/29227354/current-views-on-the-pathogenesis-of-sjgren-s-syndrome
#1
Elena Pontarini, Davide Lucchesi, Michele Bombardieri
PURPOSE OF REVIEW: The purpose of this review is to provide an insight into the pathophysiological mechanisms involved in the pathogenesis of primary Sjgren's Syndrome (pSS), highlighting recent findings with potential therapeutic repercussions. RECENT FINDINGS: In the last 2 years, epigenetic analyses provided new insights into pSS pathogenesis. Characterization of DNA methylation patterns, chromatin structures and microRNA confirmed the importance of aberrant interferon and B-cell responses in the development of the disease...
December 8, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/29223395/a-novel-mouse-model-for-tracking-the-fate-of-cxcr5-expressing-t-cells
#2
Tomo Takebe, Kazuki Sakamoto, Yoshikazu Higami, Yohsuke Harada
The germinal center (GC) reaction, a critical process in the humoral immune response, requires follicular helper T (Tfh) cells. Tfh cells express the master transcription factor Bcl6 and chemokine receptor CXCR5, which enable them to migrate from the T cell zone to B cell follicles and interact with GC B cells. However, CXCR5 is downregulated when Tfh cells become memory cells. Therefore, it is difficult to track Tfh cells continuously in vivo. In this study, we generated a mouse strain, Cxcr5CreERT2R26Tomato, in which the fluorescent protein tdTomato is inducibly expressed in CXCR5+ cells by tamoxifen administration...
December 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29215459/complete-b-cell-deficiency-reduces-allograft-inflammation-and-intragraft-macrophages-a-rat-kidney-transplant-model
#3
Sarah E Panzer, Nancy A Wilson, Bret M Verhoven, Ding Xiang, C Dustin Rubinstein, Robert R Redfield, Weixiong Zhong, Shannon R Reese
BACKGROUND: Increasingly it is being appreciated that B cells have broad roles beyond the humoral response, and are able to contribute to and regulate inflammation. The specific role of B cells in the pathogenesis of early allograft inflammation remains unclear. METHODS: To address this question, we generated B cell deficient Lewis rats via CRISPR technology. In a full mismatch transplant model, kidneys from Brown Norway donors were transplanted into B cell deficient Lewis recipients (B) or wild type Lewis recipients...
December 5, 2017: Transplantation
https://www.readbyqxmd.com/read/29212910/foxp1-negatively-regulates-t-follicular-helper-cell-differentiation-and-germinal-center-responses-by-controlling-cell-migration-and-ctla-4
#4
Bi Shi, Jianlin Geng, Yin-Hu Wang, Hairong Wei, Beth Walters, Wei Li, Xuerui Luo, Anna Stevens, Melanie Pittman, Bin Li, Sunnie R Thompson, Hui Hu
T follicular helper (Tfh) cells play an essential role in the formation of germinal centers (GC) and generation of high-affinity Abs. The homing of activated CD4+ T cells into B cell follicles and the involvement of key costimulatory and coinhibitory molecules are critical in controlling both the initiation and the magnitude of GC responses. Meanwhile, studies have shown that a high number of single clone B cells leads to intraclonal competition, which inhibits the generation of high-affinity Abs. Our previous work has shown that transcription factor Foxp1 is a critical negative regulator of Tfh cell differentiation...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29212666/stat4-and-t-bet-control-follicular-helper-t-cell-development-in-viral-infections
#5
Jason S Weinstein, Brian J Laidlaw, Yisi Lu, Jessica K Wang, Vincent P Schulz, Ningcheng Li, Edward I Herman, Susan M Kaech, Patrick G Gallagher, Joe Craft
Follicular helper T (Tfh) cells promote germinal center (GC) B cell survival and proliferation and guide their differentiation and immunoglobulin isotype switching by delivering contact-dependent and soluble factors, including IL-21, IL-4, IL-9, and IFN-γ. IL-21 and IFN-γ are coexpressed by Tfh cells during viral infections, but transcriptional regulation of these cytokines is not completely understood. In this study, we show that the T helper type 1 cell (Th1 cell) transcriptional regulators T-bet and STAT4 are coexpressed with Bcl6 in Tfh cells after acute viral infection, with a temporal decline in T-bet in the waning response...
December 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29202179/extensively-reorganized-systemic-lymph-nodes-provide-a-feasible-environment-for-self-reactivity-in-lupus-prone-nzb-nzw-f1-mice
#6
Yoichi Kurosawa, Madoka Ozawa, Yasuhiro Kanda, Arata Takeuchi, Toshihiko Kawamura, Ichiei Narita, Tomoya Katakai
Lymphadenopathy is a frequently observed symptom in systemic lupus erythematosus, although the immunological role of lymph nodes (LNs) in systemic autoimmunity remains largely unknown. Here, we performed comprehensive and systematic analyses of LNs in lupus-prone NZB × NZW F1 (BWF1) mice, demonstrating extensive tissue reorganization of the systemic LNs with follicular expansion, hyper germinal center (GC) formation, atrophy of the paracortical T cell area, and expansion of the medulla in aged BWF1 mice bearing glomerulonephritis...
November 30, 2017: International Immunology
https://www.readbyqxmd.com/read/29200102/adult-primary-immune-thrombocytopenia-spleen-histology-findings-and-outcomes-according-to-rituximab-use-based-on-analysis-of-41-cases
#7
Adeline Furudoï, Étienne Rivière, Estibaliz Lazaro, Enio Furudoï, Jean-François Viallard, Marie Parrens
Immune thrombocytopenia (ITP) is an acquired antibody-mediated disease, for which splenectomy remains a curative treatment. We analyzed histology and phenotypes of ITP-splenectomy specimens from 41 adult patients, with different previous ITP-specific treatments, including B-cell-depleting rituximab (RTX) or not, in an attempt to predict splenectomy success or failure on the basis of day 56 postoperative platelet counts. RTX-naive ITP-spleen samples, compared with those from a 20-patient control trauma cohort, contained the following nonspecific, ITP-evocative, white-pulp lesions: follicular helper T-cell (programmed death-1 and inducible T-cell COStimulator) expansion in reactive follicles (P=0...
December 1, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29196729/peripheral-t-follicular-helper-cells-make-a-difference-in-hiv-reservoir-size-between-elite-controllers-and-patients-on-successful-cart
#8
Marcial García, Miguel Górgolas, Alfonso Cabello, Vicente Estrada, José Manuel Ligos, Manuel Fernández-Guerrero, Carlos Barros, Juan Carlos López-Bernaldo, Francisco Javier De La Hera, María Montoya, José Miguel Benito, Norma Rallón
HIV latency is the main barrier to HIV eradication. Peripheral T follicular helper (pTfh) cells have a prominent role in HIV persistence. Herein, we analyzed the HIV reservoir size within memory CD4+ T-cell subsets in patients with HIV replication control. Twenty HIV-infected patients with suppressed HIV replication were included, with 10 elite controllers (EC) and 10 treated (TX) individuals. The HIV reservoir size was analyzed in resting memory CD4+ T-cells (Trm), pTfh, and non-pTfh cells using an ultrasensitive digital-droplet-PCR assay...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29196451/late-arising-t-follicular-helper-cells-cultivate-the-b-cell-crop-during-chronic-infections
#9
REVIEW
Shannon M Kahan, Allan J Zajac
Follicular helper CD4+ T cells are essential for the development of neutralizing antibodies that contain chronic viral infection.
December 1, 2017: Science Immunology
https://www.readbyqxmd.com/read/29196450/migratory-cd11b-conventional-dendritic-cells-induce-t-follicular-helper-cell-dependent-antibody-responses
#10
Jayendra Kumar Krishnaswamy, Uthaman Gowthaman, Biyan Zhang, Johan Mattsson, Louis Szeponik, Dong Liu, Renee Wu, Theresa White, Samuele Calabro, Lan Xu, Magalie A Collet, Marina Yurieva, Samuel Alsén, Per Fogelstrand, Anne Walter, William R Heath, Scott N Mueller, Ulf Yrlid, Adam Williams, Stephanie C Eisenbarth
T follicular helper (Tfh) cells are a subset of CD4+ T cells that promote antibody production during vaccination. Conventional dendritic cells (cDCs) efficiently prime Tfh cells; however, conclusions regarding which cDC instructs Tfh cell differentiation have differed between recent studies. We found that these discrepancies might exist because of the unusual sites used for immunization in murine models, which differentially bias which DC subsets access antigen. We used intranasal immunization as a physiologically relevant route of exposure that delivers antigen to all tissue DC subsets...
December 1, 2017: Science Immunology
https://www.readbyqxmd.com/read/29196449/sustained-t-follicular-helper-cell-response-is-essential-for-control-of-chronic-viral-infection
#11
Ute Greczmiel, Nike Julia Kräutler, Alessandro Pedrioli, Ilka Bartsch, Paola Agnellini, Gregor Bedenikovic, James Harker, Kirsten Richter, Annette Oxenius
During chronic viral infections, both CD8 and CD4 T cell responses are functionally compromised. Alongside exhaustion of CD8 T cells during chronic viral infections, it has also been documented that the CD4 T cells have an increased propensity to differentiate toward CXCR5+ T follicular helper cell (TFH) lineage. Whether these TFH cells contribute to the immune response to chronic viral infection has remained unclear. Using chronic lymphocytic choriomeningitis virus (LCMV) infection in conjunction with an in vivo system where TFH cells can be conditionally ablated, we have established that these TFH cells do in fact play an important protective function...
December 1, 2017: Science Immunology
https://www.readbyqxmd.com/read/29192177/up-regulation-of-interleukin-21-contributes-to-liver-pathology-of-schistosomiasis-by-driving-gc-immune-responses-and-activating-hscs-in-mice
#12
Yanyan Wang, Cai Lin, Yun Cao, Zhongliang Duan, Zhixun Guan, Jing Xu, Xing-Quan Zhu, Chaoming Xia
The pathology of schistosome egg-induced liver granuloma, fibrosis and eventually liver scarring is complicated. CD4+ helper T (Th) cells play critical roles in both host humoral immunity and cellular immunity against parasitic infection and immunopathology in schistosomiasis. Follicular helper T (Tfh) cells are another specialized subset of Th cells and involved in infectious diseases. However, the immune regulatory mechanism of Tfh cells in severe liver pathology of schistosomiasis is still poorly understood...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29186193/rig-i-like-receptor-activation-by-dengue-virus-drives-follicular-t-helper-cell-formation-and-antibody-production
#13
Joris K Sprokholt, Tanja M Kaptein, John L van Hamme, Ronald J Overmars, Sonja I Gringhuis, Teunis B H Geijtenbeek
Follicular T helper cells (TFH) are fundamental in orchestrating effective antibody-mediated responses critical for immunity against viral infections and effective vaccines. However, it is unclear how virus infection leads to TFH induction. We here show that dengue virus (DENV) infection of human dendritic cells (DCs) drives TFH formation via crosstalk of RIG-I-like receptor (RLR) RIG-I and MDA5 with type I Interferon (IFN) signaling. DENV infection leads to RLR-dependent IKKε activation, which phosphorylates IFNα/β receptor-induced STAT1 to drive IL-27 production via the transcriptional complex ISGF3...
November 29, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29181005/induction-of-robust-b-cell-responses-after-influenza-mrna-vaccination-is-accompanied-by-circulating-hemagglutinin-specific-icos-pd-1-cxcr3-t-follicular-helper-cells
#14
Gustaf Lindgren, Sebastian Ols, Frank Liang, Elizabeth A Thompson, Ang Lin, Fredrika Hellgren, Kapil Bahl, Shinu John, Olga Yuzhakov, Kimberly J Hassett, Luis A Brito, Hugh Salter, Giuseppe Ciaramella, Karin Loré
Modified mRNA vaccines have developed into an effective and well-tolerated vaccine platform that offers scalable and precise antigen production. Nevertheless, the immunological events leading to strong antibody responses elicited by mRNA vaccines are largely unknown. In this study, we demonstrate that protective levels of antibodies to hemagglutinin were induced after two immunizations of modified non-replicating mRNA encoding influenza H10 encapsulated in lipid nanoparticles (LNP) in non-human primates. While both intradermal (ID) and intramuscular (IM) administration induced protective titers, ID delivery generated this response more rapidly...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29180490/identity-and-diversity-of-human-peripheral-th-and-t-regulatory-cells-defined-by-single-cell-mass-cytometry
#15
Matthew A Kunicki, Laura C Amaya Hernandez, Kara L Davis, Rosa Bacchetta, Maria-Grazia Roncarolo
Human CD3+CD4+ Th cells, FOXP3+ T regulatory (Treg) cells, and T regulatory type 1 (Tr1) cells are essential for ensuring peripheral immune response and tolerance, but the diversity of Th, Treg, and Tr1 cell subsets has not been fully characterized. Independent functional characterization of human Th1, Th2, Th17, T follicular helper (Tfh), Treg, and Tr1 cells has helped to define unique surface molecules, transcription factors, and signaling profiles for each subset. However, the adequacy of these markers to recapitulate the whole CD3+CD4+ T cell compartment remains questionable...
November 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29163552/t-follicular-helper-cells-as-a-new-target-for-immunosuppressive-therapies
#16
REVIEW
Lin Yan, Kitty de Leur, Rudi W Hendriks, Luc J W van der Laan, Yunying Shi, Lanlan Wang, Carla C Baan
Over the past decade, antibody-mediated (humoral) rejection has been recognized as a common cause of graft dysfunction after organ transplantation and an important determinant for graft loss. In humoral alloimmunity, T follicular helper (Tfh) cells play a crucial role, because they help naïve B cells to differentiate into memory B cells and alloantibody-producing plasma cells within germinal centers. In this way, they contribute to the induction of donor-specific antibodies, which are responsible for the humoral immune response to the allograft...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163509/downregulated-il-21-response-and-t-follicular-helper-cell-exhaustion-correlate-with-compromised-cd8-t-cell-immunity-during-chronic-toxoplasmosis
#17
Magali M Moretto, SuJin Hwang, Imtiaz A Khan
CD8 T cells are important for maintaining the chronicity of Toxoplasma gondii infection. In a T. gondii encephalitis susceptible model, we recently demonstrated that CD4 T cells play an essential helper role in the maintenance of the effector response and CD8 T cell dysfunctionality was linked to CD4 T cell exhaustion. However, CD4 T cells are constituted of different subsets with various functions and the population(s) providing help to the CD8 T cells has not yet been determined. In the present study, T follicular helper cells (Tfh), which are known to be essential for B cell maturation and are one of the main sources of IL-21, were significantly increased during chronic toxoplasmosis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163507/impact-of-chronic-viral-infection-on-t-cell-dependent-humoral-immune-response
#18
REVIEW
Stéphane Rodriguez, Mikaël Roussel, Karin Tarte, Patricia Amé-Thomas
During the last decades, considerable efforts have been done to decipher mechanisms supported by microorganisms or viruses involved in the development, differentiation, and function of immune cells. Pathogens and their associated secretome as well as the continuous inflammation observed in chronic infection are shaping both innate and adaptive immunity. Secondary lymphoid organs are functional structures ensuring the mounting of adaptive immune response against microorganisms and viruses. Inside these organs, germinal centers (GCs) are the specialized sites where mature B-cell differentiation occurs leading to the release of high-affinity immunoglobulin (Ig)-secreting cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163465/b-cell-activating-factor-and-the-b-cell-compartment-in-hiv-siv-infection
#19
REVIEW
Gwenoline Borhis, Maria Trovato, Nada Chaoul, Hany M Ibrahim, Yolande Richard
With the goal to design effective HIV vaccines, intensive studies focused on broadly neutralizing antibodies, which arise in a fraction of HIV-infected people. Apart from identifying new vulnerability sites in the viral envelope proteins, these studies have shown that a fraction of these antibodies are produced by self/poly-reactive B-cells. These findings prompted us to revisit the B-cell differentiation and selection process during HIV/SIV infection and to consider B-cells as active players possibly shaping the helper T-cell program within germinal centers (GCs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29141217/th1-like-plasmodium-specific-memory-cd4-t-cells-support-humoral-immunity
#20
Ryan A Zander, Rahul Vijay, Angela D Pack, Jenna J Guthmiller, Amy C Graham, Scott E Lindner, Ashley M Vaughan, Stefan H I Kappe, Noah S Butler
Effector T cells exhibiting features of either T helper 1 (Th1) or T follicular helper (Tfh) populations are essential to control experimental Plasmodium infection and are believed to be critical for resistance to clinical malaria. To determine whether Plasmodium-specific Th1- and Tfh-like effector cells generate memory populations that contribute to protection, we developed transgenic parasites that enable high-resolution study of anti-malarial memory CD4 T cells in experimental models. We found that populations of both Th1- and Tfh-like Plasmodium-specific memory CD4 T cells persist...
November 14, 2017: Cell Reports
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