Dennis Clement, Edina K Szabo, Silje Zandstra Krokeide, Merete Thune Wiiger, Marianna Vincenti, Daniel Palacios, Young-Tae Chang, Christian Grimm, Sandip Patel, Harald Stenmark, Andreas Brech, Rakesh Kumar Majhi, Karl-Johan Malmberg
Cytotoxic lymphocytes eliminate cancer cells through the release of lytic granules, a specialized form of secretory lysosomes. This compartment is part of the pleomorphic endolysosomal system and is distinguished by its highly dynamic Ca2+ signaling machinery. Several transient receptor potential (TRP) calcium channels play essential roles in endolysosomal Ca2+ signaling and ensure the proper function of these organelles. In this study, we examined the role of TRPML1 (TRP cation channel, mucolipin subfamily, member 1) in regulating the homeostasis of secretory lysosomes and their cross-talk with mitochondria in human NK cells...
September 22, 2023: Journal of Immunology
Amanpreet Kaur, Avrokin Surnilla, Anita J Zaitouna, Michael B Mumphrey, Venkatesha Basrur, Irina Grigorova, Marcin Cieslik, Mary Carrington, Alexey I Nesvizhskii, Malini Raghavan
The extreme polymorphisms of HLA class I proteins result in structural variations in their peptide binding sites to achieve diversity in Ag presentation. External factors could independently constrict or alter HLA class I peptide repertoires. Such effects of the assembly factor tapasin were assessed for HLA-B*44:05 (Y116) and a close variant, HLA-B*44:02 (D116), which have low and high tapasin dependence, respectively, for their cell surface expression. Analyses of the HLA-B*44:05 peptidomes in the presence and absence of tapasin reveal that peptides with C-terminal tryptophans and higher predicted affinities are preferentially selected by tapasin, coincident with reduced frequencies of peptides with other C-terminal amino acids, including leucine...
September 22, 2023: Journal of Immunology
Xiangyang Wang, Xiangyu Chen, Jierong Chen, Chunhui Liao, Xiaofan Yang, Jiasheng Zhou, Shanshan Liu, Shusen Ye, Yuhao Zheng, Linzi Huang, Jiacong Zhao, Lilin Ye, Bihui Huang, Yingjiao Cao
Ever-growing evidence has revealed that group 2 innate lymphoid cells (ILC2s) exhibit pleiotropic effects in antihelminth immunity, allergy, tissue protection, and cancer. Currently, the role of ILC2s in cancer is highly controversial regarding the intricate tumor microenvironment (TME), and the tumor-promoting or antitumor immunological mechanisms of ILC2s remain largely unknown. In this study, we report that dopamine receptor 1 (DRD1) restrains ILC2 activity in the TME. DRD1 deficiency promotes ILC2 activation, which irritates eosinophil recruitment and cytotoxic CD8+ T cell expansion during ongoing malignancy...
September 20, 2023: Journal of Immunology
Jing Wang, Zhuo-Qian Zhang, Francis Gigliotti, Terry W Wright
High levels of IFN-γ are produced in the lung during an adaptive immune response to Pneumocystis, but the effects of this prototypical Th1 cytokine on fungal clearance and immunopathogenesis have not been fully defined. Therefore, Pneumocystis-infected immunodeficient mice were immune reconstituted and administered control or anti-IFN-γ neutralizing Ab to determine how IFN-γ regulates the balance between host defense and immune-mediated lung injury. Mice treated with anti-IFN-γ demonstrated an initial worsening of Pneumocystis pneumonia-related immunopathogenesis, with greater weight loss, heightened lung inflammation, and more severe pulmonary function deficits than control mice...
September 18, 2023: Journal of Immunology
Alex Pellerin, Ying Tan, Simon Lu, Ramon G Bonegio, Ian R Rifkin
Gain-of-function polymorphisms in the transcription factor IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing systemic lupus erythematosus. Global homozygous or heterozygous deficiency of IRF5 from birth confers protection in many lupus mouse models. However, less is known about the effects of IRF5 targeting after autoimmunity has already developed. This is an important point to clarify when considering IRF5 as a potential therapeutic target in lupus. In this study, we demonstrate that genetic reduction of IRF5 expression after disease initiation reduces disease severity in the FcγRIIB-/- Y-linked autoimmune accelerating mouse lupus model...
September 18, 2023: Journal of Immunology
Bei Jia, Chenchen Zhao, Kentaro Minagawa, Hiroko Shike, David F Claxton, W Christopher Ehmann, Witold B Rybka, Shin Mineishi, Ming Wang, Todd D Schell, K Sandeep Prabhu, Robert F Paulson, Yi Zhang, Leonard D Shultz, Hong Zheng
Allogeneic hematopoietic stem cell transplantation (alloSCT) is, in many clinical settings, the only curative treatment for acute myeloid leukemia (AML). The clinical benefit of alloSCT greatly relies on the graft-versus-leukemia (GVL) effect. However, AML relapse remains the top cause of posttransplant death; this highlights the urgent need to enhance GVL. Studies of human GVL have been hindered by the lack of optimal clinically relevant models. In this article, we report, the successful establishment of a novel (to our knowledge) humanized GVL model system by transplanting clinically paired donor PBMCs and patient AML into MHC class I/II knockout NSG mice...
September 15, 2023: Journal of Immunology
Nancy Monson, Chad Smith, Hannah Greenberg, Patricia Plumb, Alyssa Guzman, Key Tse, Ding Chen, Wei Zhang, Miles Morgan, Haley Speed, Craig Powell, Sushobhna Batra, Lindsay Cowell, Scott Christley, Steve Vernino, Kyle Blackburn, Benjamin Greenberg
Pediatric and adult autoimmune encephalitis (AE) are often associated with Abs to the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor (NMDAR). Very little is known regarding the cerebrospinal fluid humoral immune profile and Ab genetics associated with pediatric anti-NMDAR-AE. Using a combination of cellular, molecular, and immunogenetics tools, we collected cerebrospinal fluid from pediatric subjects and generated 1) flow cytometry data to calculate the frequency of B cell subtypes in the cerebrospinal fluid of pediatric subjects with anti-NMDAR-AE and controls, 2) a panel of recombinant human Abs from a pediatric case of anti-NMDAR-AE that was refractory to treatment, and 3) a detailed analysis of the Ab genes that bound the NR1 subunit of the NMDAR...
September 15, 2023: Journal of Immunology
Jin Yuan, Ping Tong, Zhongliang Wang, Xiaoqian Xu, Xiaoli Zhao, Xuanyi Meng, Yong Wu, Xin Li, Jinyan Gao, Hongbing Chen
Staphylococcus aureus enterotoxin B (SEB), one of the most common bacterial toxins in food contamination, has been poorly understood in relationship to food allergy outcomes. To investigate whether the ingestion of enterotoxins in food allergens could affect the development of food allergy, OVA-sensitized female BALB/c mice were challenged with OVA added with different doses of SEB or LPS. Allergic symptoms, such as diarrhea rate and hypothermia, could be aggravated in mice challenged with OVA and a low dose of SEB...
September 13, 2023: Journal of Immunology
Roxroy C Morgan, Cameron Frank, Munmun Greger, Mary Attaway, Mikael Sigvardsson, Elizabeth T Bartom, Barbara L Kee
IFN-γ-producing invariant NKT (iNKT)1 cells are lipid-reactive innate-like lymphocytes that are resident in the thymus and peripheral tissues where they protect against pathogenic infection. The thymic functions of iNKT1 cells are not fully elucidated, but subsets of thymic iNKT cells modulate CD8 T cell, dendritic cell, B cell, and thymic epithelial cell numbers or function. In this study, we show that a subset of murine thymic iNKT1 cells required TGF-β-induced signals for their postselection development, to maintain hallmark TGF-β-induced genes, and for expression of the adhesion receptors CD49a and CD103...
September 13, 2023: Journal of Immunology
Ivan Mwebaza, Rachel Shaw, Qing Li, Shane Fletcher, Jacqueline M Achkar, Clifford V Harding, Stephen M Carpenter, W Henry Boom
Mycobacterium tuberculosis cell-wall glycolipids such as mannosylated lipoarabinomannan (ManLAM) can inhibit murine CD4+ T cells by blocking TCR signaling. This results in suppression of IL-2 production, reduced T cell proliferation, and induction of CD4+ T cell anergy. This study extended these findings to the interaction between primary human CD4+ T cells and macrophages infected by mycobacteria. Exposure of human CD4+ T cells to ManLAM before activation resulted in loss of polyfunctionality, as measured by IL-2, IFN-γ, and TNF-α expression, and reduced CD25 expression...
September 11, 2023: Journal of Immunology
Françoise Morin, Noopur Singh, Julius Baya Mdzomba, Aline Dumas, Alexandre Patenaude, Vincent Pernet, Luc Vallières
We thank the McGill Integrated Core for Animal Modeling at the Goodman Cancer Research Centre, Montreal, for providing services for the creation of the conditional Hdc knockout mouse line.
September 11, 2023: Journal of Immunology
Linxia Zhang, Anli Zhang, Xinyu Zhu, Xinmei Tian, Jiaohan Guo, Qian He, Lingyan Zhu, Songhua Yuan, Chen Zhao, Xiaoyan Zhang, Jianqing Xu
A better understanding of the regulatory mechanisms governing the development of memory CD8+ T cells could provide instructive insights into vaccination strategies and T cell-based immunotherapies. In this article, we showed that CD160 surface protein is required for CD8+ T cell memory formation. In the response to acute lymphocytic choriomeningitis virus infection in a mouse model, CD160 ablation resulted in the failure of the development of all three memory CD8+ T cell subsets (central, effective, and tissue-resident memory), concomitant with a skewed differentiation into short-lived effector T cells...
September 11, 2023: Journal of Immunology
Hongguang Zhang, Xin Li, Yiwei Wang, Xianxian Liu, Jing Guo, Zheng Wang, Lulu Zhang, Sidong Xiong, Chunsheng Dong
Activation of the mitochondrial antiviral signaling (MAVS) adaptor, also known as IPS-1, VISA, or Cardif, is crucial for antiviral immunity in retinoic acid-inducible gene I (RIG-I)-like receptor signaling. Upon interacting with RIG-I, MAVS undergoes K63-linked polyubiquitination by the E3 ligase Trim31, and subsequently aggregates to activate downstream signaling effectors. However, the molecular mechanisms that modulate MAVS activation are not yet fully understood. In this study, the mitochondrial solute carrier SLC25A23 was found to attenuate type I IFN antiviral immunity using genome-wide CRISPR/Cas9 screening...
September 11, 2023: Journal of Immunology
Russell Whelan, Andrew Feemster, Jennifer Laskowski, Brandon Renner, Liudmila Kulik, Felix Poppelaars, Cameron Lee, V Michael Holers, Joshua M Thurman
B cell-targeted therapies are effective for treating multiple different kidney diseases in humans and also protect mice from Adriamycin nephropathy. Because glomerular IgM is frequently seen in both humans and mice with "nonimmune" forms of glomerular disease, we hypothesized that natural IgM binds to epitopes displayed in the injured glomerulus, exacerbating injury. To test this hypothesis, we induced Adriamycin nephropathy in BALB/C mice that cannot secrete soluble IgM (sIgM-/- mice) and compared them with BALB/C controls...
September 8, 2023: Journal of Immunology
Jesus Zamora-Pineda, Olga Kalinina, Anne I Sperling, Katherine L Knight
Intestinal inflammatory diseases affect millions of people worldwide, and one class of drugs showing promise toward treatment of several inflammatory diseases is probiotics. Numerous studies have been performed using probiotics to prevent and treat intestinal inflammatory diseases. Most of these studies used intact bacteria, and neither the active molecule nor the molecular mechanisms by which they affect immune responses are known. We have shown that the probiotic Bacillus subtilis is anti-inflammatory and can protect mice from acute colitis induced by the enteric pathogen Citrobacter rodentium...
September 6, 2023: Journal of Immunology
Tyler J M Jordan, Jinbo Chen, Ning Li, Susan Burette, Li Wan, Liuqing Chen, Donna A Culton, Songmei Geng, Paul Googe, Nancy E Thomas, Luis A Diaz, Zhi Liu
Bullous pemphigoid (BP) is the most common autoimmune bullous skin disease of humans and is characterized by eosinophilic inflammation and circulating and tissue-bound IgG and IgE autoantibodies directed against two hemidesmosomal proteins: BP180 and BP230. The noncollagenous 16A domain (NC16A) of BP180 has been found to contain major epitopes recognized by autoantibodies in BP. We recently established the pathogenicity of anti-NC16A IgE through passive transfer of patient-derived autoantibodies to double-humanized mice that express the human high-affinity IgE receptor, FcεRI, and human NC16A domain (FcεRI/NC16A)...
September 6, 2023: Journal of Immunology
Derek Miller, Roberto Romero, Luke Myers, Yi Xu, Marcia Arenas-Hernandez, Jose Galaz, Cinque Soto, Bogdan Done, Angelica Quiroz, Awoniyi O Awonuga, David R Bryant, Adi L Tarca, Nardhy Gomez-Lopez
T cells are implicated in the pathophysiology of preterm labor and birth, the leading cause of neonatal morbidity and mortality worldwide. Specifically, maternal decidual T cells infiltrate the chorioamniotic membranes in chronic chorioamnionitis (CCA), a placental lesion considered to reflect maternal anti-fetal rejection, leading to preterm labor and birth. However, the phenotype and TCR repertoire of decidual T cells in women with preterm labor and CCA have not been investigated. In this study, we used phenotyping, TCR sequencing, and functional assays to elucidate the molecular characteristics and Ag specificity of T cells infiltrating the chorioamniotic membranes in women with CCA who underwent term or preterm labor...
August 30, 2023: Journal of Immunology
Emma G M Tondeur, Jane S A Voerman, Mitchell A A Geleijnse, Laure S van Hofwegen, Anneloes van Krimpen, Julia Koerner, Gunja Mishra, Ziye Song, Christopher Schliehe
The induction of CTL responses by vaccines is important to combat infectious diseases and cancer. Biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres and synthetic long peptides are efficiently internalized by professional APCs and prime CTL responses after cross-presentation of Ags on MHC class I molecules. Specifically, they mainly use the cytosolic pathway of cross-presentation that requires endosomal escape, proteasomal processing, and subsequent MHC class I loading of Ags in the endoplasmic reticulum (ER) and/or the endosome...
August 28, 2023: Journal of Immunology
Chi Ma, Justin McCallen, John C McVey, Rajiv Trehan, Kylynda Bauer, Qianfei Zhang, Benjamin Ruf, Sophie Wang, Chunwei Walter Lai, Giorgio Trinchieri, Jay A Berzofsky, Firouzeh Korangy, Tim F Greten
The gut microbiome is an important modulator of the host immune system. In this study, we found that altering the gut microbiome by oral vancomycin increases liver invariant NKT (iNKT) cell function. Enhanced iNKT cytokine production and activation marker expression were observed in vancomycin-treated mice following both Ag-specific and Ag-independent in vivo iNKT stimulations, with a more prominent effect in the liver than in the spleen. Fecal transplantation studies demonstrated that the iNKT functional regulation is mediated by altering the gut microbiome but uncoupled from the modulation of iNKT cell population size...
August 25, 2023: Journal of Immunology
Haiyan Zhang, Jiapei Liu, Yiming Sun, Junwei Huang, Hanzhou Qi, Ruoyang Shao, Qiaoyuan Wu, QianLi Jiang, Rong Fu, Qifa Liu, Hua Jin
Chronic graft-versus-host disease (cGVHD) involves multiple organs, but little is known about bone marrow (BM) alterations caused by cGVHD. In mice and humans, we found that cGVHD is associated with BM fibrosis resulting in T cell infiltration, IgG deposition, and hematopoietic dysfunction. Macrophages and Nestin+ mesenchymal stromal cells (MSCs) participated in the process of BM fibrosis during BM cGVHD development. BM macrophage numbers were significantly increased in mice and humans with BM fibrosis associated with cGVHD...
August 23, 2023: Journal of Immunology
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.