bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-Inflammatory Role of IL-17 in Experimental Autoimmune Uveitis
Authors: Ke Yan , Liu Ke , Huang Guo-Qiang , Cui Yan , Kaplan Henry J. , Shao Hui , Sun Deming 
Published: February 2009

Abstract
Previous studies have shown that IL-17 is a strong proinflammatory cytokine and that IL-17-producing autoreactive T cells play a major role in the pathogenesis of autoimmune diseases. In a previous study, we showed that injection of experimental autoimmune uveitis-susceptible mice with anti-IL-17 Abs blocked subsequent disease development. To determine whether administration of IL-17 to experimental autoimmune uveitis-susceptible Lewis rats and B10RIII mice injected with disease-inducing peptides enhanced disease susceptibility, we injected the recipient animals with various doses of human rIL-17 (hIL-17). Unexpectedly, the treated animals showed significant amelioration of disease; in addition, both the intensity of the autoreactive response and cytokine production by the autoreactive T cells induced by immunization with uveitogenic peptides were significantly decreased. Our results show that IL-17 has anti-inflammatory activity and that this cytokine can suppress the development of autoimmune disease.
c-Abl Kinase Is Required for β2 Integrin-Mediated Neutrophil Adhesion
Authors: Cui Lingling , Chen Cuixia , Xu Ting , Zhang Juechao , Shang Xin , Luo Jixian , Chen Liang , Ba Xueqing , Zeng Xianlu 
Published: February 2009

Abstract
Integrin regulation in neutrophil adhesion is essential for innate immune response. c-Abl kinase is a nonreceptor tyrosine kinase and is critical for signaling transduction from various receptors in leukocytes. Using neutrophils and dHL-60 (neutrophil-like differentiation of HL-60) cells, we show that c-Abl kinase is activated by β2 integrin engagement and is required for β2 integrin-dependent neutrophil sustained adhesion and spreading. The expression of β2 integrin on neutrophils induced by TNF-α is not affected by c-Abl kinase inhibitor STI571, suggesting that c-Abl kinase is not involved in TNF-α-induced integrin activation. The recruitment of c-Abl kinase to β2 integrin is dependent on talin head domain, which constitutively interacts with β2 integrin cytoplasmic domain. After activated, c-Abl kinase increases the tyrosine phosphorylation of Vav. The SH3 domain of c-Abl kinase is involved in its interaction with talin and Vav. Thus, c-Abl kinase plays an essential role in the activation of Vav induced by β2 integrin ligation and in regulating neutrophil-sustained adhesion and spreading.
Reciprocal Interactions between Commensal Bacteria and γδ Intraepithelial Lymphocytes during Mucosal Injury
Authors: Ismail Anisa S. , Behrendt Cassie L. , Hooper Lora V. 
Published: February 2009

Abstract
The intestinal mucosal surface is in direct contact with a vast beneficial microbiota. The symbiotic nature of this relationship is threatened when the surface epithelium is injured, yet little is known about how mucosal surfaces maintain homeostasis with commensal microbes following damage. γδ Intraepithelial lymphocytes (γδ IEL) reside at the gut epithelial surface, where they stimulate mucosal healing following acute injury. A genome-wide analysis of the γδ IEL response to dextran sulfate sodium-induced colonic damage revealed induction of a complex transcriptional program, including coordinate regulation of cytoprotective, immunomodulatory, and antibacterial factors. Studies in germfree mice demonstrated that commensal microbiota regulate key components of this transcriptional program, thus revealing a dialogue between commensal bacteria and γδ IEL in injured epithelia. Analysis of TCRδ-deficient mice indicated that γδ T cells are essential for controlling mucosal penetration of commensal bacteria immediately following dextran sulfate sodium-induced damage, suggesting that a key function of γδ IEL is to maintain host-microbial homeostasis following acute mucosal injury. Taken together, these findings disclose a reciprocal relationship between γδ T cells and intestinal microbiota that promotes beneficial host-microbial relationships in the intestine.
Induction of IDO by Bacille Calmette-Guérin Is Responsible for Development of Murine Depressive-Like Behavior
Authors: O'Connor Jason C. , Lawson Marcus A. , André Caroline , Briley Eileen M. , Szegedi Sandra S. , Lestage Jacques , Castanon Nathalie , Herkenham Miles , Dantzer Robert , Kelley Keith W. 
Published: February 2009

AbstractChronic inflammation activates the tryptophan-degrading enzyme IDO, which is well known to impair T cell proliferation. We have previously established that bacille Calmette-Guérin (BCG), an attenuated form of Mycobacterium bovis, is associated with persistent activation of IDO in the brain and chronic depressive-like behavior, but a causative role has not been established. In these experiments we used both pharmacologic and genetic approaches to test the hypothesis that IDO activation is responsible for the development of chronic depression that follows BCG infection. BCG induced TNF-α, IFN-γ, and IDO mRNA steady-state transcripts in the brain as well as the enzyme 3-hydroxyanthranilic acid oxygenase (3-HAO) that lies downstream of IDO and generates the neuroactive metabolite, quinolinic acid. Behaviors characteristic of depression were apparent 1 wk after BCG infection. Pretreatment with the competitive IDO inhibitor 1-methyltryptophan fully blocked BCG-induced depressive-like behaviors. Importantly, IDO-deficient mice were completely resistant to BCG-induced depressive-like behavior but responded normally to BCG induction of proinflammatory cytokines. These results are the first to prove that the BCG-induced persistent activation of IDO is accompanied by the induction of 3-hydroxyanthranilic acid oxygenase and that IDO is required as an initial step for the subsequent development of chronic depressive-like behavior.
The Essential Role of Single Ig IL-1 Receptor-Related Molecule/Toll IL-1R8 in Regulation of Th2 Immune Response
Authors: Bulek Katarzyna , Swaidani Shadi , Qin Jinzhong , Lu Yi , Gulen Muhammet F. , Herjan Tomasz , Min Booki , Kastelein Robert A. , Aronica Mark , Kosz-Vnenchak Magdalena , Li Xiaoxia 
Published: February 2009

Abstract
A novel cytokine IL-33, an IL-1 family member, signals via ST2 receptor and promotes Th2 responses, through the activation of NF-κB and MAP kinases. Previous studies reported that single Ig IL-1R-related molecule (SIGIRR)/Toll IL-1R8 acts as negative regulator for TLR-IL-1R-mediated signaling. We now found that SIGIRR formed a complex with ST2 upon IL-33 stimulation and specifically inhibited IL-33/ST2-mediated signaling in cell culture model. Furthermore, IL-33-induced Th2 response was enhanced in SIGIRR-deficient mice compared with that in wild-type control mice, suggesting a negative regulatory role of SIGIRR in IL-33/ST2 signaling in vivo. Similar to ST2, SIGIRR was highly expressed in in vitro polarized Th2 cells, but not Th1 cells. SIGIRR-deficient Th2 cells produce higher levels of Th2 cytokines, including IL-5, IL-4, and IL-13, than that in wild-type cells. Moreover, SIGIRR-deficient mice developed stronger Th2 immune response in OVA-challenged asthma model. Taken together, our results suggest that SIGIRR plays an important role in the regulation of Th2 response in vivo, possibly through its impact on IL-33-ST2-mediated signaling.
Rapid Dendritic Cell Mobilization to the Large Intestinal Epithelium Is Associated with Resistance to Trichuris muris Infection
Authors: Cruickshank Sheena M. , Deschoolmeester Matthew L. , Svensson Marcus , Howell Gareth , Bazakou Aikaterini , Logunova Larisa , Little Matthew C. , English Nicholas , Mack Matthias , Grencis Richard K. , Else Kathryn J. , Carding Simon R. 
Published: February 2009

Abstract
The large intestine is a major site of infection and disease, yet little is known about how immunity is initiated within this site and the role of dendritic cells (DCs) in this process. We used the well-established model of Trichuris muris infection to investigate the innate response of colonic DCs in mice that are inherently resistant or susceptible to infection. One day postinfection, there was a significant increase in the number of immature colonic DCs in resistant but not susceptible mice. This increase was sustained at day 7 postinfection in resistant mice when the majority of the DCs were mature. There was no increase in DC numbers in susceptible mice until day 13 postinfection. In resistant mice, most colonic DCs were located in or adjacent to the epithelium postinfection. There were also marked differences in the expression of colonic epithelial chemokines in resistant mice and susceptible mice. Resistant mice had significantly increased levels of epithelium-derived CCL2, CCL3, CCL5, and CCL20 compared with susceptible mice. Furthermore, administering neutralizing CCL5 and CCL20 Abs to resistant mice prevented DC recruitment. This study provides clear evidence of differences in the kinetics of DC responses in hosts inherently resistant and susceptible to infection. DC responses in the colon correlate with resistance to infection. Differences in the production of DC chemotactic chemokines by colonic epithelial cells in response to infection in resistant vs susceptible mice may explain the different kinetics of the DC response.
Acute, but Not Resolved, Influenza A Infection Enhances Susceptibility to House Dust Mite-Induced Allergic Disease
Authors: Al-Garawi Amal A. , Fattouh Ramzi , Walker Tina D. , Jamula Erin B. , Botelho Fernando , Goncharova Susanna , Reed Jennifer , Stampfli Martin R. , O'Byrne Paul M. , Coyle Anthony J. , Jordana Manel 
Published: February 2009

Abstract
The impact of respiratory viral infections on the emergence of the asthmatic phenotype is a subject of intense investigation. Most experimental studies addressing this issue have used the inert Ag OVA with controversial results. We examined the consequences of exposure to a low dose of the common aeroallergen house dust mite (HDM) during the course of an influenza A infection. First, we delineated the kinetics of the immune-inflammatory response in the lung of mice following intranasal infection with influenza A/PR8/34. Our data demonstrate a peak response during the first 10 days, with considerable albeit not complete resolution at day 39 postinfection (p.i.). At day 7 p.i., mice were exposed, intranasally, to HDM for 10 consecutive days. We observed significantly enhanced eosinophilic inflammation, an expansion in Th2 cells, enhanced HDM-specific IgE and IgG1 responses and increased mucous production. Furthermore, lung mononuclear cells produced enhanced IFN-γ and IL-5, unchanged IL-13, and reduced IL-4. These immunologic and structural changes lead to marked lung dysfunction. This allergic phenotype occurs at a time when there is a preferential increase in plasmacytoid dendritic cells over myeloid dendritic cells, activated CD8+ T cells, and increased IFN-γ production, all of which have been proposed to inhibit allergic responses. In contrast, the inflammatory response elicited by HDM was reduced when exposure occurred during the resolution phase (day 40 p.i.). Interestingly, this was not associated with a reduction in sensitization. Thus, the proinflammatory environment established during an acute influenza A infection enhances Th2-polarized immunity to a low dose of HDM and precipitates marked lung dysfunction.
IL-3 Induces Basophil Expansion In Vivo by Directing Granulocyte-Monocyte Progenitors to Differentiate into Basophil Lineage-Restricted Progenitors in the Bone Marrow and by Increasing the Number of Basophil/Mast Cell Progenitors in the Spleen
Authors: Ohmori Keitaro , Luo Yuchun , Jia Yi , Nishida Jun , Wang Zhengqi , Bunting Kevin D. , Wang Demin , Huang Hua 
Published: February 2009

Abstract
Recent work has established important roles for basophils in regulating immune responses. To exert their biological functions, basophils need to be expanded to critical numbers. However, the mechanisms underlying basophil expansion remain unclear. In this study, we established that IL-3 played an important role in the rapid and specific expansion of basophils. We found that the IL-3 complex (IL-3 plus anti-IL-3 Ab) greatly facilitated the differentiation of GMPs into basophil lineage-restricted progenitors (BaPs) but not into eosinophil lineage-restricted progenitors or mast cells in the bone marrow. We also found that the IL-3 complex treatment resulted in ∼4-fold increase in the number of basophil/mast cell progenitors (BMCPs) in the spleen. IL-3-driven basophil expansion depended on STAT5 signaling. We showed that GMPs but not common myeloid progenitors expressed low levels of IL-3 receptor. IL-3 receptor expression was dramatically up-regulated in BaPs but not eosinophil lineage-restricted progenitors. Approximately 38% of BMCPs expressed the IL-3Rα-chain. The up-regulated IL-3 receptor expression was not affected by IL-3 or STAT5. Our findings demonstrate that IL-3 induced specific expansion of basophils by directing GMPs to differentiate into BaPs in the bone marrow and by increasing the number of BMCPs in the spleen.
The Levels of Retinoic Acid-Inducible Gene I Are Regulated by Heat Shock Protein 90-α
Authors: Matsumiya Tomoh , Imaizumi Tadaatsu , Yoshida Hidemi , Satoh Kei , Topham Matthew K. , Stafforini Diana M. 
Published: February 2009

Abstract
Retinoic acid-inducible gene I (RIG-I) is an intracellular pattern recognition receptor that plays important roles during innate immune responses to viral dsRNAs. The mechanisms and signaling molecules that participate in the downstream events that follow activation of RIG-I are incompletely characterized. In addition, the factors that define intracellular availability of RIG-I and determine its steady-state levels are only partially understood but are likely to play a major role during innate immune responses. It was recently reported that the antiviral activity of RIG-I is negatively regulated by specific E3 ubiquitin ligases, suggesting participation of the proteasome in the regulation of RIG-I levels. In this study, we used immunoprecipitation combined with mass spectrometry to identify RIG-I-interacting proteins and found that RIG-I forms part of a protein complex that includes heat shock protein 90-α (HSP90-α), a molecular chaperone. Biochemical studies using purified systems demonstrated that the association between RIG-I and HSP90-α is direct but does not involve participation of the CARD domain. Inhibition of HSP90 activity leads to the dissociation of the RIG-I-HSP90 complex, followed by ubiquitination and proteasomal degradation of RIG-I. In contrast, the levels of RIG-I mRNA are unaffected. Our studies also show that the ability of RIG-I to respond to stimulation with polyinosinic:polycytidylic acid is abolished when its interaction with HSP90 is inhibited. These novel findings point to HSP90-α as a chaperone that shields RIG-I from proteasomal degradation and modulates its activity. These studies identify a new mechanism whose dysregulation may seriously compromise innate antiviral responses in mammals.
Differential Migration of Epidermal and Dermal Dendritic Cells during Skin Infection
Authors: Eidsmo Liv , Allan Rhys , Caminschi Irina , van Rooijen Nico , Heath William R. , Carbone Francis R. 
Published: February 2009

Abstract
Dendritic cells (DCs) are extremely heterogeneous, most evident in the skin where a variety of different subsets have been identified in recent years. DCs of healthy skin include a number of distinct populations in the dermal layer as well as the well-characterized Langerhans cells (LCs) of the epidermis. These steady-state populations are augmented during bouts of local inflammation by additional monocyte-derived DCs. In an effort to better understand the distinction between the different subsets, we examined their behavior following skin infection with HSV. LC emigration rapidly followed appearance of virus in the skin and resulted in depopulation of regions in areas surrounding infected nerve endings. A separate DC population was found to accumulate within the dermis under patches of active epidermal infection with at least some derived from blood monocyte precursors. Ag-positive DCs could occasionally be found in these dermal accumulations, although they represented a minority of DCs in these areas. In addition, infected DCs appeared compromised in their trafficking capabilities and were largely absent from the migrating population. On resolution of skin disease, LCs repopulated the reformed epidermis and these were of mixed origin, with around half entering from the circulation and the remainder derived from local progenitors. Overall, our results show a range of migrational complexities between distinct skin DC populations as a consequence of localized infection.
Transgenic Inhibition of Astroglial NF-κB Improves Functional Outcome in Experimental Autoimmune Encephalomyelitis by Suppressing Chronic Central Nervous System Inflammation
Authors: Brambilla Roberta , Persaud Trikaldarshi , Hu Xianchen , Karmally Shaffiat , Shestopalov Valery I. , Dvoriantchikova Galina , Ivanov Dmitry , Nathanson Lubov , Barnum Scott R. , Bethea John R. 
Published: February 2009

AbstractIn the CNS, the transcription factor NF-κB is a key regulator of inflammation and secondary injury processes. Following trauma or disease, the expression of NF-κB-dependent genes is activated, leading to both protective and detrimental effects. In this study, we show that transgenic inactivation of astroglial NF-κB (glial fibrillary acidic protein-IκBα-dominant-negative mice) resulted in reduced disease severity and improved functional recovery following experimental autoimmune encephalomyelitis. At the chronic stage of the disease, transgenic mice exhibited an overall higher presence of leukocytes in spinal cord and brain, and a markedly higher percentage of CD8+CD122+ T regulatory cells compared with wild type, which correlated with the timing of clinical recovery. We also observed that expression of proinflammatory genes in both spinal cord and cerebellum was delayed and reduced, whereas the loss of neuronal-specific molecules essential for synaptic transmission was limited compared with wild-type mice. Furthermore, death of retinal ganglion cells in affected retinas was almost abolished, suggesting the activation of neuroprotective mechanisms. Our data indicate that inhibiting NF-κB in astrocytes results in neuroprotective effects following experimental autoimmune encephalomyelitis, directly implicating astrocytes in the pathophysiology of this disease.
Temporal Changes in Myeloid Cells in the Cervix during Pregnancy and Parturition
Authors: Timmons Brenda C. , Fairhurst Anna-Marie , Mahendroo Mala S. 
Published: February 2009

Abstract
Preterm birth occurs at a rate of 12.7% in the U.S. and is the primary cause of fetal morbidity in the first year of life as well as the cause of later health problems. Elucidation of mechanisms controlling cervical remodeling is critical for development of therapies to reduce the incidence of prematurity. The cervical extracellular matrix must be disorganized during labor to allow birth, followed by a rapid repair postpartum. Leukocytes infiltrate the cervix before and after birth and are proposed to regulate matrix remodeling during cervical ripening via release of proteolytic enzymes. In the current study, flow cytometry and cell sorting were used to determine the role of immune cells in cervical matrix remodeling before, during, and after parturition. Markers of myeloid cell differentiation and activation were assessed to define phenotype and function. Tissue monocytes and eosinophils increased in the cervix before birth in a progesterone-regulated fashion, whereas macrophage numbers were unchanged. Neutrophils increased in the postpartum period. Increased mRNA expression of Csfr1 and markers of alternatively activated M2 macrophages during labor or shortly postpartum suggest a function of M2 macrophages in postpartum tissue repair. Changes in cervical myeloid cell numbers are not reflected in the peripheral blood. These data along with our previous studies suggest that myeloid-derived cells do not orchestrate processes required for initiation of cervical ripening before birth. Additionally, macrophages with diverse phenotypes (M1 and M2) are present in the cervix and are most likely involved in the postpartum repair of tissue.
Engagement of CD83 on B Cells Modulates B Cell Function In Vivo
Authors: Kretschmer Birte , Lüthje Katja , Schneider Stefanie , Fleischer Bernhard , Breloer Minka 
Published: February 2009

Abstract
The transmembrane glycoprotein CD83 is an important regulator of both thymic T cell maturation and peripheral T cell response. Recent studies suggested that CD83 is also involved in the regulation of B cell maturation, activation, and homeostasis. In this study, we show that in vivo overexpression of CD83 dose dependently interfered with the Ig response to thymus-dependent and thymus-independent model Ag immunization. CD83 deficiency, in contrast, which was restricted to B cells in mixed bone marrow chimeras, led to unchanged or even slightly increased Ig responses. Strikingly, the engagement of CD83 that is naturally up-regulated on wild-type B cells by injection of anti-CD83 mAb in vivo induced a 100-fold increase in the IgG1 response to immunization. Kinetic analysis revealed that CD83 had to be engaged simultaneously or shortly after the B cell activation through injection of Ag, to modulate the IgG1 secretion. Furthermore, using mixed bone marrow chimeras in which either selectively the B cells or the dendritic cells were CD83 deficient, we demonstrate that anti-CD83 mAb mediated its biologic effect by engaging CD83 on B cells and not on CD11c+ dendritic cells. Taken together, we provide strong evidence that CD83 transduces regulatory signals into the very B cell on which it is expressed.
Cutting Edge: The Foxp3 Target miR-155 Contributes to the Development of Regulatory T Cells
Authors: Kohlhaas Susan , Garden Oliver A. , Scudamore Cheryl , Turner Martin , Okkenhaug Klaus , Vigorito Elena 
Published: February 2009

Abstract
Foxp3 is a transcription factor that is essential for the normal development of regulatory T cells (Tregs). In the absence of microRNAs (miRNAs), Foxp3+ Tregs develop but fail to maintain immune homeostasis, leading to a scurfy-like disease. Global analysis of the network of genes regulated by Foxp3 has identified the miRNA miR-155, which is highly expressed in Tregs, as a direct target of Foxp3. In this study we report that miR-155-deficient mice have reduced numbers of Tregs, both in the thymus and periphery, due to impaired development. However, we found no evidence for defective suppressor activity of miR-155-deficient Tregs, either in vitro or in vivo. Our results indicate that miR-155 contributes to Treg development, but that additional miRNAs control Treg function.