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Journal of Leukocyte Biology

Yao Yao, Yan Zhang, Min Shi, Yueyue Sun, Chong Chen, Mingshan Niu, Qi Zhang, Lingyu Zeng, Ruosi Yao, Hujun Li, Jiajia Yang, Zhenyu Li, Kailin Xu
The treatment of multiple myeloma (MM) with bortezomib (BTZ) is promising; however, the emergence of resistance is challenging in the clinical treatment. Thus, a novel targeted treatment or exploring the mechanism underlying BTZ resistance is an urgent requisite. The current data showed that high expression of USP7 in myeloma was a predictor of short overall survival and poor outcome. USP7 knockout significantly suppressed the colony formation, inhibited the proliferation of BTZ-resistant MM cells even in the presence of growth factors, and overcame BTZ resistance...
July 19, 2018: Journal of Leukocyte Biology
Youssra Haouami, Tarak Dhaouadi, Imen Sfar, Mongi Bacha, Tahar Gargah, Rafika Bardi, Ezzeddine Abderrahim, Rym Goucha, Taïeb Ben Abdallah, Yousr Gorgi
Th17 cell subset has been implicated in autoimmune diseases, tumor immunity and, transplant rejection. In order to investigate the role of IL-17/IL-23 pathway in allograft outcome, intragraft expression of IL-17 mRNA and single nucleotide polymorphisms (SNPs) of IL-17A, IL-17F, IL-17RC, and IL23R genes were evaluated with a quantification of IL-17A, IL-17F, and IL-23 plasma levels. This study revealed that recipients with acute rejection (AR) had a significant increase in IL-17A mRNA expression levels after transplantation compared to controls (P = 0...
July 19, 2018: Journal of Leukocyte Biology
José Carlos Santos, Petr Broz
Guanylate-binding proteins (GBPs) are conserved family of IFN-inducible GTPases that play an important role in the host immunity against bacterial, viral, and protozoan pathogens. GBPs protect the host by associating with intracellular microbes, their vacuolar niche or, in the case of viruses, with their replication complex. This association results in a restriction of the respective pathogen, yet the exact molecular mechanisms of the antimicrobial functions of GBPs are still unclear. Recent work has linked the GBPs with the activation of inflammasomes, multi-protein complexes that assemble upon recognition of pathogen- or host-derived signals and that drive the release of cytokines and host cell death...
July 18, 2018: Journal of Leukocyte Biology
Tanya Fradin, Edna Bechor, Yevgeny Berdichevsky, Iris Dahan, Edgar Pick
A central event in the activation of the phagocyte NADPH oxidase involves binding of p67phox to the dehydrogenase region of Nox2. The identity of the binding site in Nox2 is unknown. By measuring binding of p67phox to synthetic Nox2 peptides, we previously identified a sequence corresponding to Nox2 residues 357-383, as a potential binding site. A key role was attributed to a 369 Cys-Gly-Cys371 triad, shared by peptides 357-371 (peptide 24) and 369-383 (peptide 28). In this study, we show that (1) oxidation of cysteines in peptides 24 and 28 by a variety of oxidants markedly enhances the binding of p67phox ; (2) replacing cysteines by arginine abolishes the response to oxidants and the enhanced binding of p67phox ; (3) oxidants act by generating an intramolecular disulfide bond linking cysteines 369 and 371, generating such bond during peptide synthesis reproduces the effect of oxidants; (4) for the disulfide bond to lead to enhanced binding, cysteines must be separated by an intervening residue; bonds joining adjacent cysteines, or cysteines located on two peptides, do not enhance binding; (5) dissociating disulfide bonds by reducing agents abolishes enhanced binding; (6) treating p67phox with the alkylating agent N-ethylmaleimide suppresses binding; and (7) mutating all nine cysteines in p67phox to serines abolishes binding and diminishes the ability of p67phox to support NADPH oxidase activation in vitro...
July 16, 2018: Journal of Leukocyte Biology
Jorge Dominguez-Andres, Mihai G Netea
During the last few years, a growing body of evidence has shown that immunological memory is not an exclusive trait of lymphocytes, as many inflammatory insults can alter the functionality and the responsiveness of the innate immune system in the long term. Innate immune cells, such as monocytes, macrophages, dendritic cells, and NK cells can be influenced by the encounters with inflammatory stimuli, undergoing functional reprogramming and developing changed responses to subsequent chellenges. The long-term reprogramming depends on the rewiring of cell metabolism and epigenetic processes, and they stay at the basis of induction of both innate immune memory (also termed trained immunity) and innate immune tolerance...
July 12, 2018: Journal of Leukocyte Biology
Ming-Shi Chang, Yu-Hsiang Hsu
Chronic kidney disease and its complications are a major public health problem worldwide. Diabetic nephropathy has become the main contributing cause of terminal renal failure. There are now evidences that different inflammatory molecules, including proinflammatory cytokines, play a critical role in the development of microvascular diabetic complications, including nephropathy. IL-20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory disorders likes psoriasis, atherosclerosis, and renal failure...
July 12, 2018: Journal of Leukocyte Biology
Massimo Gadina, Catrina Johnson, Daniella Schwartz, Michael Bonelli, Sarfaraz Hasni, Yuka Kanno, Paul Changelian, Arian Laurence, John J O'Shea
In this era, it is axiomatic that cytokines have critical roles in cellular development and differentiation, immune homeostasis, and host defense. Equally, dysregulation of cytokines is known to contribute to diverse inflammatory and immune-mediated disorders. In fact, the past 20 years have witnessed the rapid translation of basic discoveries in cytokine biology to multiple successful biological agents (mAbs and recombinant fusion proteins) that target cytokines. These targeted therapies have not only fundamentally changed the face of multiple immune-mediated diseases but have also unequivocally established the role of specific cytokines in human disease; cytokine biologists have many times over provided remarkable basic advances with direct clinical benefit...
July 12, 2018: Journal of Leukocyte Biology
Hashini M Batugedara, Jiang Li, Gang Chen, Dihong Lu, Jay J Patel, Jessica C Jang, Kelly C Radecki, Abigail C Burr, David D Lo, Adler R Dillman, Meera G Nair
Resistin-like molecule α (RELMα) is a highly secreted protein in type 2 (Th2) cytokine-induced inflammation including helminth infection and allergy. In infection with Nippostrongylus brasiliensis (Nb), RELMα dampens Th2 inflammatory responses. RELMα is expressed by immune cells, and by epithelial cells (EC); however, the functional impact of immune versus EC-derived RELMα is unknown. We generated bone marrow (BM) chimeras that were RELMα deficient (RELMα-/ - ) in BM or non BM cells and infected them with Nb...
July 10, 2018: Journal of Leukocyte Biology
Kyle K Payne, Hussein F Aqbi, Savannah E Butler, Laura Graham, Rebecca C Keim, Wen Wan, Michael O Idowu, Harry D Bear, Xiang-Yang Wang, Masoud H Manjili
Conventional APCs that express MHC class II (MHCII) and co-stimulatory molecules include dendritic cells (DCs) and macrophages. Beyond these conventional APCs, immune stimulatory cells have been more recently shown to extend to a class of atypical APCs, composed of mast cells, basophils, and eosinophils. Here, we describe a unique type of APC, Gr1-/low CD11b-/low cells with a granularity and size characteristic of myeloid cells and with the ability to present Ag for crosspresentation. These cells constitutively express MHCII and the costimulatory molecules, CD80, CD86, and CD40...
July 9, 2018: Journal of Leukocyte Biology
Rebecca M Baron, Min-Young Kwon, Ana P Castano, Sailaja Ghanta, Dario F Riascos-Bernal, Silvia Lopez-Guzman, Alvaro Andres Macias, Bonna Ith, Scott L Schissel, James A Lederer, Raymond Reeves, Shaw-Fang Yet, Matthew D Layne, Xiaoli Liu, Mark A Perrella
High mobility group (HMG) proteins are a family of architectural transcription factors, with HMGA1 playing a role in the regulation of genes involved in promoting systemic inflammatory responses. We speculated that blocking HMGA1-mediated pathways might improve outcomes from sepsis. To investigate HMGA1 further, we developed genetically modified mice expressing a dominant negative (dn) form of HMGA1 targeted to the vasculature. In dnHMGA1 transgenic (Tg) mice, endogenous HMGA1 is present, but its function is decreased due to the mutant transgene...
July 5, 2018: Journal of Leukocyte Biology
Xiaoyi Yuan, Nathaniel Berg, Jae Woong Lee, Thanh-Thuy Le, Viola Neudecker, Na Jing, Holger Eltzschig
MicroRNAs were discovered more than 2 decades ago and have profound impact on diverse biological processes. Specific microRNAs have important roles in modulating the innate immune response and their dysregulation has been demonstrated to contribute to inflammatory diseases. MiR-223 in particular, is very highly expressed and tightly regulated in hematopoietic cells. It functions as key modulator for the differentiation and activation of myeloid cells. The central role of miR-223 in myeloid cells, especially neutrophil and macrophage differentiation and activation has been studied extensively...
July 3, 2018: Journal of Leukocyte Biology
Jörg J Goronzy, Bin Hu, Chulwoo Kim, Rohit R Jadhav, Cornelia M Weyand
T cells are a heterogeneous population of cells that differ in their differentiation stages. Functional states are reflected in the epigenome that confers stability in cellular identity and is therefore important for naïve as well as memory T cell function. In many cellular systems, changes in chromatin structure due to alterations in histone expression, histone modifications and DNA methylation are characteristic of the aging process and cause or at least contribute to cellular dysfunction in senescence...
June 27, 2018: Journal of Leukocyte Biology
Alessandra Nerviani, Costantino Pitzalis
Ectopic (or tertiary) lymphoid structures (ELS) are organized aggregates of lymphocytes resembling secondary lymphoid organs and developing in chronically inflamed nonlymphoid tissues during persistent infections, graft rejection, autoimmune conditions, and cancer. In this review, we will first depict the mechanisms regulating ELS generation, focusing on the role played by lymphoid chemokines. We will then characterize ELS forming in target organs during autoimmune conditions, here exemplified by rheumatoid arthritis, and cancer, highlighting the relevance of the tissue-specific factors...
June 27, 2018: Journal of Leukocyte Biology
Jose Angel Nicolás-Ávila, Andrés Hidalgo, Iván Ballesteros
The functions of macrophages in healthy tissues extend beyond their well-established roles as immune sentinels and effectors. Among tissues, cells of the brain and heart possess unique excitatory properties that likely demand special support. Accordingly, existing evidence demonstrates that microglia in the brain has an active role in synaptic organization, control of neuronal excitability, phagocytic removal of debris, and trophic support during brain development. In the heart, recent studies suggest that cardiac macrophages are involved in the regulation of heart homeostasis by phagocytosis, production of trophic, and immune-related factors, and by forming direct contacts with cardiomyocytes to regulate electrical conduction...
June 27, 2018: Journal of Leukocyte Biology
Sena Kim, Yeonsoo Joe, Se-Ung Park, Sun Oh Jeong, Jin-Kyung Kim, Seong Hoon Park, Hyun-Ock Pae, Young-Joon Surh, Jaekyoon Shin, Hun Taeg Chung
Endotoxin tolerance develops in the late phase of sepsis to protect cells from an early hyperinflammatory response. Nonetheless, because it induces an immunosuppressive environment, patients with sepsis in its late phase are affected by secondary infections, particularly bacterial pneumonia. Here, we showed that induction of endoplasmic reticulum (ER) stress leads to activation of glycogen synthase kinase 3β (GSK-3β) and X-box-binding protein 1 (XBP-1) in an inositol-requiring enzyme 1α (IRE1α)-mediated manner, which in turn restores the inflammatory response in endotoxin-tolerant macrophages...
June 20, 2018: Journal of Leukocyte Biology
Karolina Ivičak-Kocjan, Vida Forstnerič, Gabriela Panter, Roman Jerala, Mojca Benčina
TLRs sense conserved and essential molecular components of microbes that invade multicellular organisms. The wide range of TLR agonists, differing in size and shape, is recognized either through a single or a pair of binding sites on the ectodomains of TLRs. TLR5 recognizes bacterial flagellin through two distinct binding sites on the ectodomain, the first facilitating primary binding of flagellin and the second guiding receptor dimerization necessary for signaling. The regions of flagellin recognized by TLR5 encompass key functional regions within the D1 domain of flagellin, which is also required for the assembly of functional flagella...
June 19, 2018: Journal of Leukocyte Biology
Tzu-Sheng Hsu, Ming-Zong Lai
Hypoxia-inducible factor 1α (HIF-1α) regulates cellular responses to hypoxia. However, conflicting roles for HIF-1α in the functions of regulatory T cells (Tregs) have been reported. In this review, we summarize observations on the requirement for HIF-1α for FOXP3 expression and Tregs development, as well as for HIF-1α-mediated downregulation of FOXP3 and Tregs destabilization. We also examine the association of HIF-1α with Tregs under pathogenic conditions. Based on these findings, we suggest that HIF-1α mainly plays a detrimental role in the function and stability of Tregs and that HIF-1α is disposable for the development and suppressive function of Tregs...
June 14, 2018: Journal of Leukocyte Biology
Mahdis Monajemi, Yvonne C F Pang, Saelin Bjornson, Susan C Menzies, Nico van Rooijen, Laura M Sly
This study tested the hypothesis that Malt1 deficiency in macrophages contributes to dextran sodium sulfate (DSS)-induced intestinal inflammation in Malt1-deficient mice. In people, combined immunodeficiency caused by a homozygous mutation in the MALT1 gene is associated with increased susceptibility to bacterial infections and chronic inflammation, including severe inflammation along the gastrointestinal tract. The consequences of Malt1 deficiency have largely been attributed to its role in lymphocytes, but Malt1 is also expressed in macrophages, where it is activated downstream of TLR4 and dectin-1...
June 14, 2018: Journal of Leukocyte Biology
Koji Maruta, Chikako Watanabe, Hideaki Hozumi, Chie Kurihara, Hirotaka Furuhashi, Takeshi Takajo, Yoshikiyo Okada, Kazuhiko Shirakabe, Masaaki Higashiyama, Shunsuke Komoto, Kengo Tomita, Shigeaki Nagao, Toshiaki Ishizuka, Soichiro Miura, Ryota Hokari
The enhanced recruitment of leukocytes to the inflamed colon is a key feature of ulcerative colitis (UC). The gut-specific adhesion molecules involved in leukocyte recruitment have emerged as recent therapeutic targets. Nicotine absorbed from smoking has been reported to work protectively in UC patients. Our hypothesis is that nicotine may suppress the aberrant leukocyte recruitment and colonic inflammation via the suppression of the overexpressed gut-specific adhesion molecules in the inflamed colon. To test this hypothesis, the severity of colitis and the degree of leukocyte recruitment induced by gut-specific adhesion molecules were assessed in dextran sulfate sodium (DSS) colitis mice (C57BL/6J mice treated with 3% DSS) with or without nicotine treatment...
June 14, 2018: Journal of Leukocyte Biology
Tongjie Wang, Chengxiang Xia, Yong Dong, Xiaoli Chen, Jinyong Wang, Juan Du
Trim27 (Zinc finger protein RFP) is a potential regulator of hematopoietic stem cells (HSC), yet its role in hematopoiesis remains elusive. Here, we investigated the roles of Trim27 in hematopoiesis by enforcing its expression in mouse and human hematopoietic stem and progenitor cells (HSPC). Ectopic expression of Trim27 in mouse fetal liver (FL) HSPC confers repopulating advantage with myeloid dominance. However, the number of HSC from Trim27 group was comparable with empty vector control group, indicating that overexpression of Trim27 unlikely expanded HSC...
June 13, 2018: Journal of Leukocyte Biology
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