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International Immunology

Takahiro Nagatake, Hidehiko Suzuki, So-Ichiro Hirata, Naomi Matsumoto, Yasuko Wada, Sakiko Morimoto, Ayaka Nasu, Michiko Shimojou, Mitsuo Kawano, Kentaro Ogami, Yusuke Tsujimura, Etsushi Kuroda, Norifumi Iijima, Koji Hosomi, Ken J Ishii, Tetsuya Nosaka, Yasuhiro Yasutomi, Jun Kunisawa
We previously reported that Ag85B-expressing human parainfluenza type 2 virus (Ag85B-rHPIV2) was effective as a nasal vaccine against tuberculosis in mice; however, the mechanism by which it induces an immune response remains to be investigated. In the present study, we found that organogenesis of inducible bronchus-associated lymphoid tissue (iBALT) played a role in the induction of antigen-specific T cells and IgA antibody responses in the lung of mice intranasally administered Ag85B-rHPIV2. We found that expression of Ag85B was dispensable for the development of iBALT, suggesting that HPIV2 acted as iBALT-inducing vector...
July 16, 2018: International Immunology
Yangyan Xiao, Cintia S De Paiva, Zhiyuan Yu, Rodrigo Guimaraes de Souza, De-Quan Li, Stephen C Pflugfelder
Conjunctival goblet cell loss in ocular surface diseases is accompanied by increased number of IL-12 producing antigen presenting cells (APC) and increased IFN- expression. This study tested the hypothesis that mouse conjunctival goblet cells produce biologically active retinoic acid (RA) that suppresses CD86 expression and IL-12 production by myeloid cells. We found conditioned media from cultured conjunctival goblet cells (CjCM) suppressed stimulated CD86 expression, NF-κB p65 activation and IL-12 and IFN- production in unstimulated and LPS-stimulated cultured bone marrow derived cells containing a mixed population of APCs...
July 12, 2018: International Immunology
Elvira Mass
A literature covering 150 years of research indicates that macrophages are a diverse family of professional phagocytes that continuously explore their environment, recognize and scavenge pathogens, unfit cells, cell debris as well as metabolites, and produce a large range of bioactive molecules and growth factors. A new paradigm suggests that most tissue-resident macrophages originate from fetal precursors that colonize developing organs and self-maintain independently of bone-marrow derived cells throughout life...
July 7, 2018: International Immunology
Mitsuhiro Kanamori, Hiroko Nakatsukasa, Minako Ito, Shunsuke Chikuma, Akihiko Yoshimur
T helper 1 (Th1) is one of the most stable CD4 T cell subset, and direct conversion of fully differentiated Th1 to regulatory T (Treg) cells has been poorly investigated. Here we established a culture method for inducing Foxp3 from Th1 cells of mouse and human. This is achieved simply by resting Th1 cells without TCR ligation before stimulation in the presence of transforming growth factor beta (TGF-). We named the resulting Th1-derived Foxp3+ cells Th1reg cells. Mouse Th1reg cells showed an inducible Treg-like phenotype and suppressive ability both in vitro and in vivo...
July 2, 2018: International Immunology
Sanjay Varikuti, Steve Oghumu, Gayathri Natarajan, Jennifer Kimble, Rachel H Sperling, Ellen Moretti, Mark H Kaplan, Abhay R Satoskar
No abstract text is available yet for this article.
June 25, 2018: International Immunology
Kanako Shimizu, Tomonori Iyoda, Masahiro Okada, Satoru Yamasaki, Shin-Ichiro Fujii
Most tumors employ multiple strategies to attenuate T cell-mediated immune response. In particular, immune suppression surrounding the tumor is achieved by interfering with antigen-presenting cells and effector T cells. Controlling both the tumor and the tumor microenvironment (TME) is critical for cancer treatment. Checkpoint blockade therapy can overcome tumor-induced immune suppression, but more than half of the patients fail to respond to this treatment; therefore, more effective cancer immunotherapies are needed...
June 23, 2018: International Immunology
Shogo Tanabe, Toshihide Yamashita
During brain development, the generation of neurons and glial cells is rigorously regulated by diverse mechanisms including the immune system. Dysfunction of the developing system results in the onset of neurodevelopmental disorders and psychological disorders. Recent studies have demonstrated that the immune system is implicated in brain development. As the central nervous system is physically separated from the circulatory system by the blood-brain barrier, circulating immune cells are unable to infiltrate into the brain parenchyma...
June 15, 2018: International Immunology
Kenta Iwasaki, Nana Kitahata, Takahisa Hiramitsu, Takayuki Yamamoto, Takayuki Noda, Manabu Okada, Shunji Narumi, Yoshihiko Watarai, Yuko Miwa, Kazuharu Uchida, Matsuoka Yutaka, Kosei Horimi, Takaaki Kobayashi
It is unclear to what extent follicular helper T-cell (Tfh) development and de novo donor specific HLA antibody (DSA) production could be influenced by immunosuppressive agents, particularly calcineurin inhibitor (CNI), after kidney transplantation. Here, the effects of immunosuppressive agents on Tfh-mediated B-cell activation and antibody production were investigated. In vitro circulating Tfh (cTfh; memory CD4+CXCR5+)/B-cell (CD19+) co-culture assays revealed that CNI considerably inhibited cTfh-mediated B-cell activation and IgG antibody secretion through the suppression of IL-21 and IL-2...
June 7, 2018: International Immunology
Nathaniel J Buteyn, Kavin Fatehchand, Ramasamy Santhanam, Huiqing Fang, Gino M Dettorre, Shalini Gautam, Bonnie K Harrington, Sally E Henderson, Giovanna Merchand-Reyes, Xiaokui Mo, Don M Benson, William E Carson, Sumithira Vasu, John C Byrd, Jonathan P Butchar, Susheela Tridandapani
Acute myeloid leukemia (AML) remains a significant health problem, with poor outcomes despite chemotherapy and bone-marrow transplants. Although one form of AML, acute promyelocytic leukemia (APL), is successfully treated with all-trans retinoic acid (ATRA), this drug is seemingly ineffective against all other forms of AML. Here, we show that ATRA upregulates CD38 expression on AML blasts to sufficient levels that promote antibody-mediated fratricide following the addition of anti-CD38 Daratumumab. The combination of ATRA plus Daratumumab induced Fc-dependent conjugate formation and cytotoxicity among AML blasts in vitro...
June 2, 2018: International Immunology
Tatsuma Ban, Go R Sato, Tomohiko Tamura
The transcription factor interferon regulatory factor-5 (IRF5) plays an important role in innate immune responses via the TLR-MyD88 (Toll-like receptor - myeloid differentiation primary response 88) pathway. IRF5 is also involved in the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). Recent studies have identified new regulators, both positive and negative, which act on IRF5 activation events in the TLR-MyD88 pathway such as post-translational modifications, dimerization and nuclear translocation...
May 31, 2018: International Immunology
Akio Ohta
Immunotherapy of cancer has finally materialized following the success of immune-checkpoint blockade. Since downregulation of immune-checkpoint mechanisms is beneficial in cancer treatment, it is important to ask why tumors are infamously filled with the immunosuppressive mechanisms. Indeed, immune checkpoints are physiological negative feedback mechanisms of immune activities, and the induction of such mechanisms is important in preventing excessive destruction of inflamed normal tissues. A condition commonly found in tumors and inflamed tissues is tissue hypoxia...
May 28, 2018: International Immunology
Tomoya Narita, Takeshi Nitta, Sachiko Nitta, Tadashi Okamura, Hiroshi Takayanagi
γδT cells develop in the thymus and play important roles in protection against infection and tumor development, but the mechanisms by which the thymic microenvironment supports γδT cell differentiation remain largely unclear. Skint1, a B7-related protein expressed in thymic epithelial cells, was shown to be essential for the development of mouse Vγ5Vδ1 γδT cells. The Skint family in mouse consists of 11 members, Skint1-11. Here we generated mutant mice lacking the entire genomic region that contains all of the Skint genes...
April 26, 2018: International Immunology
Shuyin Li, Jun Liu, Qing Min, Tomokatsu Ikawa, Shoya Yasuda, Yang Yang, Yan-Qing Wang, Takeshi Tsubata, Yaofeng Zhao, Ji-Yang Wang
B-1 cells are innate-like B-cell population and produce natural antibodies that contribute to the first line of host defense. There are two subsets of B-1 cells: B-1a and B-1b. B-1a cells are the main producer of poly-reactive and autoreactive natural IgM antibodies, whereas B-1b cells can respond specifically to T-cell-independent antigens. Despite the functional significance of B-1a and B-1b cells, little information is available about what regulates the development of these two subsets. We found that Kelch-like protein 14 (KLHL14) was expressed at high levels in B cells but only at low levels in a few non-lymphoid tissues...
June 26, 2018: International Immunology
Daisuke Kamimura, Takuto Ohki, Yasunobu Arima, Masaaki Murakami
The neural regulation of organs can be categorized as systemic or local. Whereas systemic regulation by the hypothalamus-pituitary-adrenal gland-mediated release of steroid hormones has been well studied, the mechanisms for local regulation have only recently emerged. Two types of local neural regulation are known, the gateway reflex and the inflammatory reflex. The gateway reflex describes a mechanism that converts regional neural stimulations into inflammatory outputs by changing the state of specific blood vessels...
June 26, 2018: International Immunology
Yuki Usui, Yasumasa Kimura, Takeshi Satoh, Naoki Takemura, Yasuo Ouchi, Hiroko Ohmiya, Kyosuke Kobayashi, Hiromi Suzuki, Satomi Koyama, Satoko Hagiwara, Hirotoshi Tanaka, Seiya Imoto, Gérard Eberl, Yukio Asami, Kosuke Fujimoto, Satoshi Uematsu
The gut is an extremely complicated ecosystem where micro-organisms, nutrients and host cells interact vigorously. Although the function of the intestine and its barrier system weakens with age, some probiotics can potentially prevent age-related intestinal dysfunction. Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131, which are the constituents of LB81 yogurt, are representative probiotics. However, it is unclear whether their long-term intake has a beneficial influence on systemic function...
June 26, 2018: International Immunology
Erika Gruber, Christa Heyward, Jody Cameron, Cynthia Leifer
Macrophages participate in immunity, tissue repair and tissue homeostasis. Activation of Toll-like receptors (TLRs) by conserved exogenous or endogenous structures initiates signaling cascades that result in the release of cytokines such as tumor necrosis factor α (TNFα). Extracellular substrate stiffness is known to regulate functions of non-immune cells through a process called mechanotransduction, yet less is known about how physical cues affect macrophage function or TLR signaling. To investigate this question, we cultured murine primary bone marrow-derived macrophages (BMMs) and RAW264...
May 24, 2018: International Immunology
Xiuyuan Lu, Masahiro Nagata, Sho Yamasaki
Macrophage-inducible C-type lectin, better known as Mincle, is a member of the C-type lectin receptor family and is encoded by Clec4e. Mincle was an orphan receptor for a long time after having been discovered as a lipopolysaccharide-induced protein, yet later an adjuvant glycolipid in mycobacteria-trehalose dimycolate-was identified as a ligand. Ligands for Mincle were also found existing in bacteria, fungi and even mammals. When confronted with foreign elements, Mincle can recognize characteristic pathogen-associated molecular patterns, mostly glycolipids, from Mycobacterium tuberculosis and other pathogens, and thus induce immune responses against infection...
May 24, 2018: International Immunology
Hisashi Kanemaru, Fumihiro Yamane, Hiroki Tanaka, Kazuhiko Maeda, Takashi Satoh, Shizuo Akira
Growing evidence has revealed that the transcription factor basic leucine zipper transcription factor ATF-like 2 (BATF2) has unique transcriptional activities, including regulating cytokines via TLR signals in macrophages, which affect mortality due to infection and cancer. On the basis of genome-wide analyses using the chromatin immunoprecipitation-sequencing technique, we found that dual-specificity phosphatase 2 (Dusp2) had a significantly lower acetyl-histone status in Batf2-/- bone marrow-derived macrophages (BMDMs) compared with wild-type (WT) BMDMs...
May 24, 2018: International Immunology
Atsuko Kayaba, Ari Itoh-Nakadai, Kunimichi Niibe, Matsuyuki Shirota, Ryo Funayama, Akiko Sugahara-Tobinai, Yi Li Wong, Masanori Inui, Keiko Nakayama, Toshiyuki Takai
Plasma cells (PCs) acquiring long lifespans in the bone marrow (BM) play a pivotal role in the humoral arm of immunological memory. The PCs reside in a special BM niche and produce antibodies against past-encountered pathogens or vaccine components for a long time. In BM, cysteine-X-cysteine (CXC) chemokine receptor type 4 (CXCR4)-expressing PCs and myeloid cells such as dendritic cells are attracted to and held by CXC chemokine ligand 12 (CXCR12)-secreting stromal cells, where survival of the PCs is supported by soluble factors such as IL-6 and APRIL (a proliferation-inducing ligand) produced by neighboring myeloid cells...
May 24, 2018: International Immunology
Scott W Canna, Raphaela Goldbach-Mansky
No abstract text is available yet for this article.
April 25, 2018: International Immunology
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