bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of glial inflammatory responses by IL-24
Authors: Burmeister Amanda Rae , Marriott Ian 
Published: January 2023

Abstract
Maintenance of an immunoquiescent environment and/or resolution of inflammation is of critical importance within the confines of the central nervous system (CNS). The cytokine IL-10 has previously been demonstrated to play a critical role in resolving inflammation within the CNS and in suppressing damaging host responses. However, little is known regarding the role played by other IL-10 family members in the control of neuroinflammation. We have previously reported that bacterially challenged glia produce IL-10 and the related cytokine IL-19 in a delayed manner, and can respond to these cytokines by upregulating the expression of suppressor of cytokine signaling 3 (SOCS3), a key anti-inflammatory response gene. More recently, we have determined that murine astrocytes can similarly express another IL-10 family member, IL-24, in a delayed manner following activation, and constitutively express both subunits of the receptor for this cytokine. Here, we have investigated the ability of glial cells to respond to IL-24 and assessed its effect on the inflammatory responses of these cells to bacterial ligands. We demonstrate that recombinant murine IL-24 (rmIL-24) elicits the rapid expression of mRNA encoding SOCS3 by primary murine astrocytes. Importantly, we have determined that pretreatment with rmIL-24 significantly limits the production of the key pro-inflammatory cytokine IL-6 by bacterially challenged astrocytes. These findings are consistent with previous reports in peripheral tissues indicating that IL-24 acts to suppress host responses and provides another potential mechanism whereby resident CNS cells can limit detrimental neuroinflammation.
Palmitate induces interleukin-8 expression in human monocytic cells via TLR4/MyD88 dependent pathway
Authors: Ahmad Rasheed , AlRoub Areej Abu , Sindhu Sardar 
Published: January 2023

Abstract
Infiltrated immune cells in adipose tissue in obesity produce various cytokines and chemokines which are involved in metabolic inflammation and insulin resistance. Obese individuals are known to have increased IL-8 plasma level and it plays an important role in metabolic disorders. Since in obesity, the levels of circulatory saturated free fatty acid palmitate are increased and modulate the expression of other cytokines and chemokines, the role of palmitate in the regulation of IL-8 in monocytic cells is not well defined. Here, we provide the evidence that palmitate induces IL-8 expression at both mRNA and protein levels in human monocytic cells (P&lt;0.05). Palmitate-mediated IL-8 secretion was suppressed either by neutralizing anti-TLR4 antibody or by genetic silencing of TLR4. Furthermore, MyD88−/− cells did not express IL-8 in response to palmitate. However, IRF3 deficiency did not affect IL-8 production. NF-κB/AP-1 activity was also elevated in palmitate-treated cells. Altogether, these results show that palmitate induces TLR4/MyD88 dependent activation of IL-8 gene expression leading to activation of NF-kB/AP1 transcription factors.
NLRP3 inflammasomes are required for MUC5AC expression induced by S100A8, S100A9 and S100A12
Authors: Chung Il Yup , Kim Karam , Kang Jin Hyun 
Published: January 2023

Abstract
S100A8, S100A9, and S100A12, damage-associated molecular pattern (DAMP) molecules, initiate and modulate local inflammation and innate immune responses. NLRP3 is a component of the innate immune system that detects danger signals. Activation of NLRP3 is known to be associated with the pathogenesis of pulmonary obstructive diseases such as asthma and COPD. We have previously demonstrated that these three S100 proteins are able to induce MUC5AC production in airway epithelial cells through activation of NF-kB and ERK pathways. In this study, we examine the involvement of NLRP3 inflammasomes in the S100 proteins-induced MUC5AC production. Treatment of NCI-H292 cells with the S100 proteins results in synthesis of NLRP3 mRNA and protein along with increased procaspase-1 and IL-1b secretion. Introduction of NLRP3 siRNA leads to a decrease in MUC5AC expression, which is also accompanied by diminished IL-1b mRNA. In addition, NLRP3 siRNA inhibits S100A12-induced activation of NF-kB. In line, MCC950, an inhibitor of NLRP3 inflammasome oligomerization, abolishes MUC5AC production, with no effect on synthesis of NLRP3 molecule. Collectively, these data suggest that NLRP3 inflammasome plays an active role in S100 protein-induced mucin production in airway epithelial cells.
Interleukin 7 promotes motility of naive T cells in the lymph node
Authors: Byrum Janie Rae , Fricke Matthew , Tafoya Justyna , Moses Melanie , Cannon Judy L 
Published: January 2023

Abstract
Naïve T cells interact with dendritic cells (DCs) in lymph nodes to become activated and effect a specific immune response. The chemokine CCL21 and lysophosphatidic acid (LPA) have both been demonstrated to be important for T cell movement within the T cell zone of the lymph node. However, the residual motility in the absence of both CCL21 signaling via CCR7 and LPA suggest that additional molecules can play a role in driving T cell movement within lymph nodes. Using two photon microscopy, we show interleukin-7 (IL-7) promotes T cell motility in vitro and in vivo, in addition to its known function as a survival factor. Blocking IL-7 signaling in the lymph node elicited a reduction in T cell speed. IL-7 treatment of primary T cells in vitro resulted in increased migration across a permeable barrier and small GTPase RhoA activation. We further demonstrate that IL-7 combines with CCL21 and LPA to promote naïve T cell motility. Our results indicate that IL-7 is a novel regulator of T cell motion in lymph nodes, in addition to its effect on T cell survival.
Inflammasomes promote the initiation of Brucella induced arthritis in an IL-18 dependent manner and mediate Brucella clearance independently of IFN-γ
Authors: Lacey Carolyn , Skyberg Jerod A 
Published: January 2023

Abstract
Brucellosis, caused by the intracellular bacterial pathogen Brucella, is a zoonotic disease for which infection of the joints is the most common focal complication in humans. The purpose of this study was to identify if Brucella activation of inflammasomes and in turn caspase1/11 activation is responsible for inducing arthritis. Here we report caspase-1/11−/− (casp1/11−/−) mice had reduced swelling, inflammation and inflammatory cytokine levels early in infection relative to wild-type “WT” mice. Later in infection, joint inflammation was similar between WT and casp1/11−/− mice, but bacterial loads and swelling were greater in casp1/11−/− joints. While IL-1Rdeficiency reduced joint swelling, this effect occurred later and was not of the same magnitude as casp1/11 deficiency, indicating an IL-1 independent role of casp1/11. Casp1/11 induced inflammation was partially dependent on IL-18, and IFN-γ levels were reduced in both casp1/11−/− and IL-18-deficient mice relative to WT mice early in infection. However, while IFN-γ and casp1/11 both played a role in controlling joint Brucella burdens, an additive effect of these deficiencies was observed indicating that the protective effects of IFN-γ and casp1/11 on bacterial clearance are not interdependent. Enhanced arthritis and musculoskeletal inflammation was observed in IFN-γ-deficient, relative to WT mice. However, neutralization of IFN-γ in casp1/11−/− mice did not result in enhanced inflammation. Collectively these data demonstrate casp1/11 induces early inflammation in an IL-18 dependent manner. Moreover, there is an IFN-γ independent role of casp1/11 in joint Brucella clearance, and casp1/11 is responsible for enhanced inflammation observed in IFN-γ-deficient mice.
The prostaglandin D2 receptor CRTH2 suppresses epithelial cell responses during intestinal helminth infection
Authors: Oyesola Oyebola Oluwakemi , Webb Lauren M , Solouki Sabrina , Pham Duc , Campioli Pamela , Cubitt Rebecca , Wojno Elia D Tait 
Published: January 2023

Abstract
Type 2 inflammation is required for expulsion of intestinal helminth parasites and is characterized by immune cell activation, type 2 cytokine production, and increased mucin production by epithelial goblet cells. Previous studies show that the prostaglandin D2 (PGD2) receptor chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) promotes type 2 inflammation in the lung via effects on immune cells, but how CRTH2 influences helminth-induced type 2 inflammation in the intestine was unclear. Here we show that CRTH2-deficient mice cleared infection with the mouse-adapted helminth parasite Nippostrongylus brasiliensis more efficiently and had increased numbers of mucin-producing goblet cells in the small intestine post-infection compared to wild type mice, despite similar levels of worm establishment. These data suggest that CRTH2 restrains goblet cell responses during intestinal helminth infection, in contrast to its pro-inflammatory role in the lung. Consistent with this idea, bone marrow-chimeric mice in which only non-hematopoietic cells lacked CRTH2 also cleared parasites more efficiently than chimeric wild type mice and had increased numbers of small intestinal goblet cells. In addition, murine small intestinal organoids that were stimulated with type 2 cytokines downregulated expression of goblet cell-associated genes following culture with PGD2. Taken together, these data suggest that the PGD2-CRTH2 pathway suppresses epithelial goblet cell responses following helminth-induced type 2 inflammation in the intestine. These findings may inform the development and use of drugs that inhibit this pathway during intestinal type 2 inflammatory disease, such as food allergy.
Broccoli-derived nanoparticle inhibits mouse colitis by activating dendritic cell AMP-activated protein kinase
Authors: Deng Zhongbin , Rong Yuan , Teng Yun , Mu Jingyao , Zhuang Xiaoying , Samykutty Abhilash , Zhang Lifeng , Yan Jun , Miller Donald , Suttles Jill , zhang huang-ge 
Published: January 2023

Abstract
The intestinal immune system is continuously exposed to massive amounts of nanoparticles derived from food. Whether nanoparticles from plants we eat daily have a role in maintaining intestinal immune homeostasis is poorly defined. Here, we present evidence supporting our hypothesis that edible nanoparticles regulate intestinal immune homeostasis by targeting DC cell. With three mouse colitis models, our data show that orally given nanoparticles isolated from broccoli extracts protect mice against colitis. Broccoli-derived nanoparticles (BDN) mediated activation of adenosine monophosphate-activated protein kinase (AMPK) in dendritic cell (DC) plays a role in not only prevention of DC activation but also induction of tolerant DCs. Adoptively transferring DCs pre-pulsed with total BDN lipids but not sulforaphane depleted BDN lipids prevented DSS induced colitis in B6 mice, supporting the role of BDN sulforaphane in the induction of DC tolerance. Adoptively transferring AMPK+/+ but not AMPK−/− DCs pre-pulsed with sulforaphane prevented DSS induced colitis in B6 mice, further supporting the DC AMPK role in sulforaphane mediated prevention of DSS induced colitis. This finding could open new preventive/therapeutic avenues to address intestinal related inflammatory diseases via activating AMPK.
IL-15 regulates IL-23 production and murine IBD-like disease
Authors: Eken Ahmet , Singh Akhilesh K , Fry Mallory , Bhise Gauri , Bettelli Estelle , Oukka Mohamed 
Published: January 2023

Abstract
Group 3 innate lymphoid cells (ILC3) have been recently implicated in various autoimmune conditions including inflammatory bowel diseases (IBD). The mechanisms by which ILC3s contibute to IBD pathogenesis remain elusive. In this study, using genetic deleletions that impact ILC3s to varying degrees we sought to determine their contribution to murine IBD development. We show that IL-23-dependent T cell-induced colitis develops independently of ILC3s. Host IL-2 receptor common γ chain (IL-2Rγc) is needed for both innate and adaptive cell-driven colitis, since its deficiency impairs colitogenic T cell proliferation, expansion and recruitment to intestines. We also provide evidence that resistance to colitis in IL-2Rγc Rag2−/− mice may occur as a result of defective IL-15R signaling, and that IL–15−/− Rag1−/− mice recapitulates the murine IBD phenotype of IL-2Rγc Rag2−/− mice. Data we presented herein demonstrates that IL-15 plays an important role in IBD pathogenesis and may contribute to gut inflammation by regulating IL-23 production of antigen presenting cells.
Down-modulation of colitis-associated colorectal cancer development by treatment with helminth-derived molecules
Authors: Terrazas Luis I , Callejas Blanca , Reyes Sandy , Ledesma-Soto Yadira , Olguín Efraín J , León-Cabrera Sonia , Rodríguez-Sosa Miriam 
Published: January 2023

Abstract
A role for chronic inflammation in tumor development has been well established and supported in both, animal and epidemiological studies. A classic association between inflammation and cancer is colitis-associated colorectal cancer (CAC). Helminth infections and helminth-derived molecules have been recognized as inducers of immunoregulation. Taenia crassiceps modulates inflammatory diseases such as type 1 diabetes, colitis, and autoimmune encephalomyelitis. Here we analyzed the pathophysiologic implication of T. crassiceps excreted/secreted (TcES) products on CAC development. CAC was induced in BALB/c mice with azoxymethane followed by 3 cycles of 2% dextran sodium sulfate exposure to elicit intestinal inflammation. After cycle 1, mice received i.p. TcES (200 μg/mouse 3-times/week) until the end of the experiment. On days 20, 40 and 68 after CAC induction mice were killed to evaluate colonic inflammation, proliferation, and tumorigenesis. Untreated mice developed tumors as early as 20 days after CAC induction and by the end of the experiment, 100% of these mice displayed tumors. In contrast, only 30% of mice receiving TcES developed tumors. Tumor numbers per mouse were significantly reduced in TcES-treated mice (4.5 tumors) versus untreated mice (14.5 tumors). Both inflammation and proliferation scores in the colon from CAC-TcES-treated mice were significantly lower than CAC-untreated mice. High levels of IL-1β, TNF-α, and IL-17 in CAC-untreated mice were down-modulated by TcES-treatment. Lower expression of COX2, β-catenin and, STAT3 activation were detected in colonic tissue from mice receiving TcES. Our data suggest a main role for TcES in generating an anti-inflammatory environment that suppresses CAC progression
Phosphorylation of SNAP-23 regulates its dynamic subcellular localization and regulated exocytosis in mast cells
Authors: Naskar Pieu , Puri Niti 
Published: January 2023

Abstract
Mast cells (MCs) play an important role in inflammatory response to pathogens and in inflammatory disorders like allergies. This role depends on their ability to release prestored mediators from secretory granules in response to some external trigger like crosslinking of FcɛRI. The membrane fusion events involved therein are mediated by SNAREs. The target-SNARE SNAP-23 has been shown to be very important for MC exocytosis, and our previous studies revealed presence of one basal (Thr102) and two induced (Ser95 and Ser120) phosphorylation sites in its linker region, whose significance was not very clear. To study the role of SNAP-23 phosphorylation in the regulation of exocytosis, GFP-tagged wildtype SNAP-23 (GFP-SNAP-23) and its phosphorylation mutants were transfected into RBL MCs, that revealed some dynamic changes in SNAP-23 membrane association immediately after activation. SNAP-23 was associated with plasma membrane in resting mast cells, however on activation, it translocated to internal LAMP-3 containing lysosomal membranes, many of which contained secretory granule cargo. This dynamic change in the membrane association of SNAP-23 in MCs may be important for mediating internal granule-granule fusions in compound exocytosis. Further studies with mutants revealed, for the first time, that the basal phosphorylation site Thr102 plays an important role in initial SNAP-23 membrane association. During exocytosis, the induced phosphorylation sites Ser95 and Ser120 regulate SNAP-23 internal membrane association and subsequently mast cell exocytosis. Hence this study reveals a novel mechanism in mast cell inflammatory response that can be a therapeutic target.
Mast cells’ interaction with Leishmania leads to effector responses in reducing initial parasite load
Authors: SELVAPANDIYAN ANGAMUTHU , Naqvi Nilofer , Ahuja Kavita , Dey Ranadhir , Nakhasi Hira L , Puri Niti 
Published: January 2023

Abstract
Mast cells (MCs) are involved in clearing invading pathogens at the skin surface and play an important role in innate and adaptive defenses. Hence they may have an important role in the control of Leishmaniasis due to the protozoa Leishmania that are inoculated by infected sandfly vector on the skin surface. It is still unclear if their contributions occur directly through active pathogen killing or antigen uptake. Our objectives were to use Leishmania donovoni the causative agent of fatal visceral Leishmaniasis and L. tropica the causative agent of cutaneous leishmaniasis for studying the interactions between the parasite and MCs to clarify if MCs are directly involved in active antigen uptake, and its clearance. We found that co-culture of Leishmania with MCs led to significant killing of L. tropica and to a lesser extent of L. donovoni. Also, while there was significant uptake of L. tropica by MCs, L. donovoni was not phagocytosed by MCs. Uptake increased with time of exposure in case of L. tropica. We also found significant generation of reactive oxygen species by MCs on co-culture with these species of Leishmania, which may contribute to their clearance. However interactions of MCs with Leishmania led to generation of MC extracellular traps comprising of DNA, histones and tryptase probably to ensnare these pathogens. These results clearly establish that MCs may contribute to host defences to Leishmania in a differential manner by actively taking up these pathogens and also by mounting effector responses for their direct clearance by extracellular and non-phagocytic means. This gives us an understanding that MCs can also be used as a target for therapeutic approaches to leishmaniasis.
Antibody-dependent NK cell control of Plasmodium falciparum infection
Authors: Hart Geoffrey T , Theorell Jakob , Tran Tuan , Arora Gunjan , Crompton Peter D , Bryceson Yenan , Long Eric O 
Published: January 2023

Abstract
Plasmodium falciparum (P.f) infection is a major cause of morbidity and mortality world-wide where symptoms and death occur as a result of the blood stage of the P.f. life cycle. To date, there is no effective blood stage malarial vaccine. Natural Killer (NK) cells are key players in the control of hematopoietic cancers and viral infections, however their role in blood stage malaria is unknown. We undertook a comprehensive analysis of NK cell phenotype and function in a cohort of subjects from a malaria clinical study in Mali, Africa. Using an unbiased analysis of different NK cell subsets, we found that ‘adaptive’ NK cells (lacking FcR gamma chain) increased with age and correlated with reduced malaria risk. Adaptive NK cells had enhanced antibody dependent cellular cytotoxicity (ADCC) function relative to other NK cell subsets. Antibodies are known to be protective in malaria, however the mechanism of this protection is still being elucidated. We hypothesized the protective mechanism of adaptive NK cells may be adaptive NK cells pairing with malaria antibodies to clear infected RBCs via ADCC. In a parallel study, we have shown that NK cells from healthy US donors can inhibit the growth of Plasmodium falciparum 3D7 strain in vitro in the presence of IgG from malaria-exposed adults. Adaptive NK cells from Mali also have enhanced ADCC to infected RBCs. This work indicates that protective antibodies may pair with the strong ADCC activity of adaptive NK cells to protect human subjects from malaria symptoms. These findings thus open a new avenue for vaccine development exploring antibody-dependent cell mediated killing of malaria parasites.
Wild mouse gut microbiome protects laboratory mice against lethal influenza virus infection and colorectal cancer
Authors: Rosshart Stephan Patrick , Vassallo Brian G. , Angeletti Davide , Hutchinson Diane S. , Morgan Andrew P. , Takeda Kazuyo , Hickman Heather D. , Ajami Nadim J. , de Villena Fernando Pardo-Manuel , Yewdell Jonathan W. , Rehermann Barbara 
Published: January 2023

Abstract
Mouse models are paramount for understanding basic immunological mechanisms, but can be limited in recapitulating human diseases. The microbiome has been identified as a main factor influencing host physiology as illustrated by many studies that disrupt or modify host-microbe interactions in laboratory mice. Differences in the gut microbiome contribute to the variability of research results obtained with genetically identical animals from different vendors. In an effort to identify an external reference that better recapitulates physiologically important interactions found in a natural habitat, we asked how far removed the gut microbiome of laboratory mice is from that of their outbred, wild-living relative. Through genetic analysis we identify the closest wild relatives to classical laboratory strains among 21 distinct populations from Europe, Asia and the Americas. We establish that their gut microbiome differs significantly from that of C57BL/6 mice from the leading breeders worldwide, and that it can be transferred and maintained over several generations under vivarium conditions. Offspring of pregnant germ-free C57BL/6 mice reconstituted with the gut microbiome of wild mice exhibit a significantly reduced inflammatory response and increased survival following influenza A virus infection. This restoration of the natural ‘microbial identity’ of laboratory mice also improved their resistance against mutagen- and inflammation-induced colorectal cancer. Collectively, these data show the beneficial effects of the wild mouse microbiome in two diseases of global relevance. They also illustrate a novel approach towards developing animal models of greater biological relevance and translational research value.