Effector and Activated T Cells Induce Preterm Labor and Birth That Is Prevented by Treatment with Progesterone.
AuthorsArenas-Hernandez M, Romero R, Xu Y, Panaitescu B, Garcia-Flores V, Miller D, Ahn H, Done B, Hassan SS, Hsu CD, Tarca AL, Sanchez-Torres C, Gomez-Lopez N
JournalJ Immunol
PubMed ID30918041
'Preterm labor commonly precedes preterm birth, the leading cause of perinatal morbidity and mortality worldwide. Most research has focused on establishing a causal link between innate immune activation and pathological inflammation leading to preterm labor and birth. However, the role of maternal effector/activated T cells in the pathogenesis of preterm ... More
Plasmodium co-infection protects against chikungunya virus-induced pathologies.
AuthorsTeo TH, Lum FM, Ghaffar K, Chan YH, Amrun SN, Tan JJL, Lee CYP, Chua TK, Carissimo G, Lee WWL, Claser C, Rajarethinam R, Rénia L, Ng LFP
JournalNat Commun
PubMed ID30254309
'Co-infection with Plasmodium and chikungunya virus (CHIKV) has been reported in humans, but the impact of co-infection on pathogenesis remains unclear. Here, we show that prior exposure to Plasmodium suppresses CHIKV-associated pathologies in mice. Mechanistically, Plasmodium infection induces IFN?, which reduces viraemia of a subsequent CHIKV infection and suppresses tissue viral ... More
Genetic Inactivation of ZCCHC6 Suppresses Interleukin-6 Expression and Reduces the Severity of Experimental Osteoarthritis in Mice.
AuthorsAnsari MY, Khan NM, Ahmad N, Green J, Novak K, Haqqi TM
JournalArthritis Rheumatol
PubMed ID30302948
'Cytokine expression is tightly regulated posttranscriptionally, but high levels of interleukin-6 (IL-6) in patients with osteoarthritis (OA) indicate that regulatory mechanisms are disrupted in this disorder. The enzyme ZCCHC6 (zinc-finger CCHC domain-containing protein 6; TUT-7) has been implicated in posttranscriptional regulation of inflammatory cytokine expression, but its role in OA ... More
MYC oncogene is associated with suppression of tumor immunity and targeting Myc induces tumor cell immunogenicity for therapeutic whole cell vaccination.
AuthorsWu X, Nelson M, Basu M, Srinivasan P, Lazarski C, Zhang P, Zheng P, Sandler AD
JournalJ Immunother Cancer
PubMed ID33757986
'MYC oncogene is deregulated in 70% of all human cancers and is associated with multiple oncogenic functions including immunosuppression in the tumor microenvironment. The role of MYC in the immune microenvironment of neuroblastoma and melanoma is investigated and the effect of targeting Myc on immunogenicity of cancer cells is evaluated.' ... More
Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge.
AuthorsPardi N, Secreto AJ, Shan X, Debonera F, Glover J, Yi Y, Muramatsu H, Ni H, Mui BL, Tam YK, Shaheen F, Collman RG, Karikó K, Danet-Desnoyers GA, Madden TD, Hope MJ, Weissman D
JournalNat Commun
PubMed ID28251988
'Monoclonal antibodies are one of the fastest growing classes of pharmaceutical products, however, their potential is limited by the high cost of development and manufacturing. Here we present a safe and cost-effective platform for in vivo expression of therapeutic antibodies using nucleoside-modified mRNA. To demonstrate feasibility and protective efficacy, nucleoside-modified ... More
Enhancement of IFN? Production by Distinct Commensals Ameliorates Salmonella-Induced Disease.
AuthorsThiemann S, Smit N, Roy U, Lesker TR, Gálvez EJC, Helmecke J, Basic M, Bleich A, Goodman AL, Kalinke U, Flavell RA, Erhardt M, Strowig T
JournalCell Host Microbe
PubMed ID28618267
'The microbiota contributes to colonization resistance against invading pathogens by competing for metabolites, producing inhibitory substances, and priming protective immune responses. However, the specific commensal bacteria that promote host resistance and immune-mediated protection remain largely elusive. Using isogenic mouse lines with distinct microbiota profiles, we demonstrate that severity of disease ... More
IFN? inhibits G-CSF induced neutrophil expansion and invasion of the CNS to prevent viral encephalitis.
AuthorsRamakrishna C, Cantin EM
JournalPLoS Pathog
PubMed ID29352287
'Emergency hematopoiesis facilitates the rapid expansion of inflammatory immune cells in response to infections by pathogens, a process that must be carefully regulated to prevent potentially life threatening inflammatory responses. Here, we describe a novel regulatory role for the cytokine IFN? that is critical for preventing fatal encephalitis after viral ... More
Yirui Capsules Alleviate Atherosclerosis by Improving the Lipid Profile and Reducing Inflammation in Apolipoprotein E-Deficient Mice.
AuthorsXu J, Xia Z, Rong S, Gao H, Yang W, Li J, Ma C, Deng Q, Huang Q, Xiao L, Huang F
JournalNutrients
PubMed ID29382111
'Atherosclerosis (AS) is the main cause of cardiovascular diseases. This study investigated Yirui (YR) capsules, whose ingredients are available in health food stores, against AS and the underlying mechanisms. Male apolipoprotein E-deficient mice fed a high-fat diet for 10 weeks developed severe aortic lesions, but YR significantly decreased the plaque ... More
Zinc Finger Protein 521 Regulates Early Hematopoiesis through Cell-Extrinsic Mechanisms in the Bone Marrow Microenvironment.
AuthorsFleenor CJ, Arends T, Lei H, Åhsberg J, Okuyama K, Kuruvilla J, Cristobal S, Rabe JL, Pandey A, Danhorn T, Straign D, Espinosa JM, Warming S, Pietras EM, Sigvardsson M, Hagman JR
JournalMol Cell Biol
PubMed ID29915154
'Zinc finger protein 521 (ZFP521), a DNA-binding protein containing 30 Krüppel-like zinc fingers, has been implicated in the differentiation of multiple cell types, including hematopoietic stem and progenitor cells (HSPC) and B lymphocytes. Here, we report a novel role for ZFP521 in regulating the earliest stages of hematopoiesis and lymphoid ... More
Induction of immunosuppressive functions and NF-?B by FLIP in monocytes.
AuthorsFiore A, Ugel S, De Sanctis F, Sandri S, Fracasso G, Trovato R, Sartoris S, Solito S, Mandruzzato S, Vascotto F, Hippen KL, Mondanelli G, Grohmann U, Piro G, Carbone C, Melisi D, Lawlor RT, Scarpa A, Lamolinara A, Iezzi M, Fassan M, Bicciato S, Blazar BR, Sahin U, Murray PJ, Bronte V
JournalNat Commun
PubMed ID30518925
'Immunosuppression is a hallmark of tumor progression, and treatments that inhibit or deplete monocytic myeloid-derived suppressive cells could promote anti-tumor immunity. c-FLIP is a central regulator of caspase-8-mediated apoptosis and necroptosis. Here we show that low-dose cytotoxic chemotherapy agents cause apoptosis linked to c-FLIP down-regulation selectively in monocytes. Enforced expression ... More
Constitutive Activation of NIK Impairs the Self-Renewal of Hematopoietic Stem/Progenitor Cells and Induces Bone Marrow Failure.
AuthorsXiu Y, Xue WY, Lambertz A, Leidinger M, Gibson-Corley K, Zhao C
JournalStem Cells
PubMed ID27733012
Previously we have shown that loss of non-canonical NF-?B signaling impairs self-renewal of hematopoietic stem/progenitor cells (HSPCs). This prompted us to investigate whether persistent activation of the non-canonical NF-?B signaling will have supportive effects on HSPC self-renewal. NF-?B-inducing kinase (NIK) is an important kinase that mainly activates the non-canonical pathway ... More
FLLL32, a curcumin analog, ameliorates intestinal injury in necrotizing enterocolitis.
AuthorsEckert J, Scott B, Lawrence SM, Ihnat M, Chaaban H
JournalJ Inflamm Res
PubMed ID28652797
Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease that primarily affects premature infants. It is characterized by inflammation and leukocyte infiltration that can progress to intestinal necrosis, perforation, systemic inflammatory response, and death. In this study, we examined the effect of FLLL32, a curcumin analog, on an NEC-like neonatal intestinal ... More
Chitosan-based nanoformulated (-)-epigallocatechin-3-gallate (EGCG) modulates human keratinocyte-induced responses and alleviates imiquimod-induced murine psoriasiform dermatitis.
Psoriasis is a chronic and currently incurable inflammatory skin disease characterized by hyperproliferation, aberrant differentiation, and inflammation, leading to disrupted skin barrier function. The use of natural agents that can abrogate these effects could be useful for the treatment of psoriasis. Earlier studies have shown that treatment of keratinocytes and ... More
Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide Exendin-4.
AuthorsGarcia-Flores V, Romero R, Miller D, Xu Y, Done B, Veerapaneni C, Leng Y, Arenas-Hernandez M, Khan N, Panaitescu B, Hassan SS, Alvarez-Salas LM, Gomez-Lopez N
JournalFront Immunol
PubMed ID29967606
Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Inflammation is causally linked to preterm birth; therefore, finding an intervention that dampens maternal and fetal inflammatory responses may provide a new strategy to prevent adverse pregnancy and neonatal outcomes. Using animal models of systemic maternal inflammation [intraperitoneal ... More
GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization.
Influenza A viruses cause life-threatening pneumonia and lung injury in the lower respiratory tract. Application of high GM-CSF levels prior to infection has been shown to reduce morbidity and mortality from pathogenic influenza infection in mice, but the mechanisms of protection and treatment efficacy have not been established. ... More
TNFa and Radioresistant Stromal Cells Are Essential for Therapeutic Efficacy of Cyclic Dinucleotide STING Agonists in Nonimmunogenic Tumors.
The cGAS-STING cytosolic DNA sensing pathway may play an integral role in the initiation of antitumor immune responses. Studies evaluating the immunogenicity of various cyclic dinucleotide (CDN) STING agonists administered by intratumoral (i.t.) injection showed potent induction of inflammation, tumor necrosis, and, in some cases, durable tumor-specific adaptive immunity. However, ... More
TUSC2 Immunogene Therapy Synergizes with Anti-PD-1 through Enhanced Proliferation and Infiltration of Natural Killer Cells in Syngeneic
AuthorsMeraz IM, Majidi M, Cao X, Lin H, Li L, Wang J, Baladandayuthapani V, Rice D, Sepesi B, Ji L, Roth JA
JournalCancer Immunol Res
PubMed ID29339375
Expression of the multikinase inhibitor encoded by the tumor suppressor gene
Associations Between Immune Phenotype and Inflammation in Murine Models of Irritant Contact Dermatitis.
Irritant contact dermatitis (ICD), the most common occupational cutaneous illness, is an acute inflammatory response caused by topical irritant exposure. Multiple factors are associated with the manifestation and severity of ICD and contribute to the lack of effective prophylactic and treatment strategies. To determine the pathomechanism of ICD caused by ... More
Impact of mRNA chemistry and manufacturing process on innate immune activation.
AuthorsNelson J, Sorensen EW, Mintri S, Rabideau AE, Zheng W, Besin G, Khatwani N, Su SV, Miracco EJ, Issa WJ, Hoge S, Stanton MG, Joyal JL
JournalSci Adv
PubMed ID32637598
Messenger RNA (mRNA) represents an attractive therapeutic modality for potentially a wide range of clinical indications but requires uridine chemistry modification and/or tuning of the production process to prevent activation of cellular innate immune sensors and a concomitant reduction in protein expression. To decipher the relative contributions of these factors ... More
Targeting the CD146/Galectin-9 axis protects the integrity of the blood-brain barrier in experimental cerebral malaria.
AuthorsDuan H, Zhao S, Xiang J, Ju C, Chen X, Gramaglia I, Yan X
JournalCell Mol Immunol
PubMed ID33203936
Cerebral malaria (CM) is a life-threatening diffuse encephalopathy caused by Plasmodium falciparum, in which the destruction of the blood-brain barrier (BBB) is the main cause of death. However, increasing evidence has shown that antimalarial drugs, the current treatment for CM, do little to protect against CM-induced BBB damage. Therefore, a ... More
Galectin-3 inhibition with belapectin combined with anti-OX40 therapy reprograms the tumor microenvironment to favor anti-tumor immunity.
AuthorsSturgill ER, Rolig AS, Linch SN, Mick C, Kasiewicz MJ, Sun Z, Traber PG, Shlevin H, Redmond WL
JournalOncoimmunology
PubMed ID33717655
Treatment with an agonist anti-OX40 antibody (aOX40) boosts anti-tumor immunity by providing costimulation and driving effector T cell responses. However, tumor-induced immune suppression contributes significantly to poor response rates to aOX40 therapy, thus combining aOX40 with other agents that relieve tumor-mediated immune suppression may significantly improve outcomes. Once such target ... More