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1.  [No title available] 
PMCID: PMC3932004  PMID: 24556395
2.  [No title available] 
PMCID: PMC3932006  PMID: 24556408
3.  [No title available] 
PMCID: PMC3932007  PMID: 24556406
4.  [No title available] 
PMCID: PMC3932008  PMID: 24556400
5.  [No title available] 
PMCID: PMC3932021  PMID: 24556411
6.  [No title available] 
PMCID: PMC3944054  PMID: 24419035
7.  [No title available] 
PMCID: PMC3944065  PMID: 24463216
8.  The Central Role of Antigen Presentation in Islets of Langerhans in Autoimmune Diabetes 
The islets of Langerhans normally contain resident antigen presenting cells (APCs), which in normal conditions are mostly represented by macrophages, with a few dendritic cells (DC). We present here the features of these islet APCs, making the point that they have a supportive function in islet homeostasis. Islet APCs express high levels of major histocompatibility complexes (MHC) molecules on their surfaces and are highly active in antigen presentation in the autoimmune diabetes of the NOD mouse: they do this by presenting peptides derived from molecules of the β-cells. These APCs also are instrumental in the localization of diabetogenic T cells into islets. The islet APC present exogenous peptides derived from secretory granules of the beta cell, giving rise to unique peptide-MHC complexes (pMHC) that activate those non-conventional T cells that bypass thymus selection.
PMCID: PMC4118295  PMID: 24556398
9.  TLRs and interferons: a central paradigm in autoimmunity 
Current opinion in immunology  2013;25(6):720-727.
Investigations into the pathogenesis of lupus have largely focused on abnormalities in components of the adaptive immune system. Despite important advances, however, the question about the origin of the pathogenic process, the primary disease trigger, and the dominance of autoantibodies against nuclear components, remained unanswered. Discoveries in the last decade have provided some resolution to these questions by elucidating the central role of nucleic acid-sensing TLRs and the attendant inflammatory response, particularly the production of type I interferons. These priming events are responsible for initiating the adaptive responses that ultimately mediate the pathogenic process.
PMCID: PMC4309276  PMID: 24246388
10.  Expanding roles for GILT in immunity 
Current opinion in immunology  2012;25(1):103-108.
Gamma-interferon-inducible lysosomal thiol reductase (GILT), a thioredoxin-related oxidoreductase, functions in MHC class II-restricted antigen processing and MHC class I-restricted cross-presentation by reducing disulfide bonds of endocytosed proteins and facilitating their unfolding and optimal degradation. However, recent reports have greatly expanded our understanding of GILT’s function. Several studies of GILT and antigen processing have shown that the influence of GILT on the peptide repertoire can alter the character of the immune response and affect central tolerance. Furthermore, a few unexpected roles for GILT have been uncovered: as a host factor for Listeria monocytogenes infection, in the maintenance of cellular glutathione levels (GSH), and possibly outside the cell, as enzymatically active GILT is secreted by activated macrophages.
PMCID: PMC4287230  PMID: 23246037
11.  Genetics of systemic lupus erythematosus: immune responses and end organ resistance to damage 
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disorder. Considerable progress has been made to delineate the genetic control of this complex disorder. In this review, selected aspects of human and mouse genetics related to SLE are reviewed with emphasis on genes that contribute to both innate and adaptive immunity and to genes that contribute directly to susceptibility to end organ damage. It is concluded that the interactions among these two major pathways will provide further insight into the pathogenesis of SLE. An interactive model of the two major pathways is proposed without emphasis on the importance of breaking tolerance to autoantigens.
PMCID: PMC4274270  PMID: 25458999
12.  A Functional Framework for Interpretation of Genetic Associations in T1D 
Current opinion in immunology  2012;24(5):516-521.
Susceptibility to type 1 diabetes is attributable to genes that link disease progression to distinct steps in immune activation, expansion, and regulation. Recent studies illustrate examples of disease-associated variants that function in multiple cell types and independent pathways, some that impact different steps of a single mechanistic pathway, and some that are functionally interactive for deterministic events in setting thresholds for immune response.
PMCID: PMC4260931  PMID: 22841349
13.  Diverse roles of non-diverse molecules: MHC Class Ib molecules in Host Defense and Control of Autoimmunity 
Current opinion in immunology  2010;23(1):104-110.
While the prime function of classical MHC I molecules is to present peptide antigens to pathogen-specific cytotoxic T cells, non-classical MHC-I antigens perform a diverse array of functions in both innate and adaptive immunity. In this review we summarize recent evidence that non -classical MHC molecules are not only recognized by pathogen-specific T cells but that they also serve as immunoregulatory molecules by stimulating a number of distinct non-conventional T cell subsets.
PMCID: PMC4254846  PMID: 20970974
14.  Th17-mediated inflammation in asthma 
Current opinion in immunology  2013;25(6):10.1016/j.coi.2013.08.002.
Asthma is a heterogeneous disease with many different phenotypes. Moderate and severe asthma phenotypes have been associated with increased neutrophils and increased Th17 cytokines, IL-17A, IL-17F, and IL-22, in the bronchoalveolar lavage fluid of patients. Th17 cytokines recruit neutrophils to the airway by increasing secretion of epithelial-derived neutrophilic chemokines. In addition, Th17 cytokines also induce mucous cell metaplasia and have pleotropic effects on airway smooth muscle resulting in airway narrowing. The role of Th17 cytokines in regulating Th2 cytokine expression and allergic airway inflammation remains unclear with conflicting reports. However, the role of Th17 cells in asthma will be answered in ongoing clinical trials with therapeutics targeting IL-17A and IL-17 receptor signaling.
PMCID: PMC3855890  PMID: 24035139
15.  Commensal microbiota and NKT cells in the control of inflammatory diseases at mucosal surfaces 
Current opinion in immunology  2013;25(6):10.1016/j.coi.2013.09.012.
PMCID: PMC3867259  PMID: 24210255
16.  The deleterious role of basophils in systemic lupus erythematosus 
Current opinion in immunology  2013;25(6):10.1016/j.coi.2013.10.003.
Systemic lupus erythematosus is a complex autoimmune disease of multifactorial origins. All compartments of the immune system appear to be affected, at least in some way, and to contribute to disease pathogenesis. Due to an escape from negative selection autoreactive T and B cells accumulate in SLE patients leading to the production of autoantibodies mainly raised against nuclear components and their subsequent deposition into target organs. We recently showed that basophils, in an IgE and IL-4 dependent manner, contribute to SLE pathogenesis by amplifying autoantibody production. Here, we summarize what we have learned about the deleterious role of basophils in lupus both in a mouse model and in SLE patients. We discuss which possible pathways could be involved in basophil activation and recruitment to secondary lymphoid organs during SLE, and how basophils may amplify autoantibody production.
PMCID: PMC3876474  PMID: 24209595
17.  T Cell Recognition of Beryllium 
Current opinion in immunology  2013;25(6):10.1016/j.coi.2013.07.012.
Chronic beryllium disease (CBD) is a granulomatous lung disorder caused by a hypersensitivity to beryllium and characterized by the accumulation of beryllium-specific CD4+ T cells in the lung. Genetic susceptibility to beryllium-induced disease is strongly associated with HLA-DP alleles possessing a glutamic acid at the 69th position of the β-chain (βGlu69). The structure of HLA-DP2, the most prevalent βGlu69-containing molecule, revealed a unique solvent-exposed acidic pocket that includes βGlu69 and represents the putative beryllium binding site. The delineation of mimotopes and endogenous self-peptides that complete the αβTCR ligand for beryllium-specific CD4+ T cells suggests a unique role of these peptides in metal ion coordination and the generation of altered self-peptides, blurring the distinction between hypersensitivity and autoimmunity.
PMCID: PMC3883670  PMID: 23978481
18.  Autoimmunity to Citrullinated Proteins and the Initiation of Rheumatoid Arthritis 
Current opinion in immunology  2013;25(6):728-735.
Clinical manifestations of rheumatoid arthritis (RA), the second most common human autoimmune disease, are primarily focused on the joints, causing disability and requiring life-long treatment to ameliorate signs and symptoms. The etiology of RA is unknown; however, important discoveries in two areas have been made which provide hope that the causal mechanisms can be identified. First, the most severe form of this disease is associated with the presence of humoral and cellular autoimmunity to citrullinated proteins and peptides. Second, in the natural history of RA, autoimmunity to citrullinated antigens appears years prior to the onset of clinically apparent disease. Herein is described a model in which to consider how these two features are linked during very early disease development.
PMCID: PMC3895448  PMID: 24215742
19.  Innate immune mechanisms in vitiligo: Danger from within 
Current opinion in immunology  2013;25(6):676-682.
Vitiligo is an autoimmune disease of the skin in which melanocytes are destroyed by antigen-specific T cells, resulting in patchy depigmentation. While adaptive immunity plays a clear role in disease progression, initiating factors are largely unknown. Many studies report that cellular stress pathways are dysregulated in melanocytes from vitiligo patients, suggesting that melanocyte-intrinsic defects participate in disease pathogenesis. Recent studies reveal that melanocyte stress generates damage-associated molecular patterns that activate innate immunity, thus connecting stress to organ-specific inflammation. Genetic studies in vitiligo support a role for stress, innate immunity, and adaptive mechanisms. Here, we discuss advances in the field that highlight how cellular stress, endogenous danger signals, and innate immune activation promote the onset of vitiligo.
PMCID: PMC3935321  PMID: 24238922
20.  Emerging Antigens Involved in Allergic Responses 
Current opinion in immunology  2013;25(6):769-774.
New allergic diseases can “emerge” because of exposure to a novel antigen, because the immune responsiveness of the subject changes, or because of a change in the behavior of the population. Novel antigens have entered the environment as new pests in the home (e.g., Asian lady beetle or stink bugs), in the diet (e.g., prebiotics or wheat isolates), or because of the spread of a biting arthropod (e.g., ticks). Over the last few years, a significant new disease has been identified, which has changed the paradigm for food allergy. Bites of the tick, Amblyomma americanum, are capable of inducing IgE antibodies to galactose-alpha-1,3-galactose, which is associated with two novel forms of anaphylaxis. In a large area of the southeastern United States, the disease of delayed anaphylaxis to mammalian meat is now common. This disease challenges many previous rules about food allergy and provides a striking model of an emerging allergic disease.
PMCID: PMC3984453  PMID: 24095162
21.  Innate lymphoid cells and allergic inflammation 
Current opinion in immunology  2013;25(6):738-744.
Group 2 innate lymphoid cells (ILC2s) play critical roles in anti-helminth immunity and airway epithelial repair. Recently, these cells have also emerged as key players in the development of allergic inflammation at multiple barrier surfaces. ILC2s arise from common lymphoid progenitors in the bone marrow, are dependent on the transcription factors RORα, GATA3 and TCF-1 and produce the type 2 cytokines IL-4, IL-5, IL-9 and/or IL-13. The epithelial cell-derived cytokines IL-25, IL-33 and TSLP regulate the activation and effector functions of ILC2s, and recent studies suggest that their responsiveness to these cytokines and other factors may depend on their tissue environment. In this review, we focus on recent advances in our understanding of how ILC2s are differentially regulated in the context of allergic inflammation and discuss the therapeutic potential of targeting ILC2s in the treatment of allergic diseases.
PMCID: PMC3989991  PMID: 24001372
22.  Natural killer T (NKT) cells in autoimmune hepatitis 
Current opinion in immunology  2013;25(6):697-703.
Natural killer T (NKT) cells represent an innate-like lymphocyte population endowed with unique antigen recognition and tissue distribution features. Their abundance in the microvascular compartments of the liver allows NKT cells to immediately respond to lipid antigens and soluble factors circulating through the portal vein system by releasing tremendous amounts of different cytokines and chemokines. Subsequently, dependent on the nature of the lipid antigen encountered as well as the accessory signal(s) provided, NKT cells not only contribute to the maintenance of immune tolerance, but also direct adverse immune reactions locally and systemically. Focusing on their potent immunomodulatory features and their interactions with various innate and adaptive immune cells, the role of NKT cells in perpetuating the loss of liver-specific immune tolerance will be discussed.
PMCID: PMC4013545  PMID: 24148235
23.  The Impact of Viral Genotype on Pathogenesis and Disease Severity: Respiratory Syncytial Virus and Human Rhinoviruses 
Current opinion in immunology  2013;25(6):761-768.
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRI) and viral death in infants. RSV disease in infants is characterized by epithelial desquamation, neutrophilic bronchiolitis and pneumonia, and obstructive pulmonary mucus. Human rhinoviruses (HRV) are by far the most common cause of symptomatic upper respiratory tract infection (URI) in people and are more recently appreciated as a significant cause of LRI. RSV and HRV are also implicated in asthma pathogenesis. Within both RSV and HRV, viral genetic differences play a role in disease severity and/or prevalence in patient populations, and viral genetic differences affect pathogenesis. Here, we review data on how viral genetic differences impact disease using RSV and HRV as examples, including effects on the host immune response. Virus genotype-phenotype relationships can be exploited in the laboratory to gain insight into mechanisms by which respiratory viruses modulate host immune responses and cause disease.
PMCID: PMC4097120  PMID: 24455766
24.  Spontaneous activation of RNA-sensing pathways in autoimmune disease 
Current opinion in immunology  2013;25(6):712-719.
Multiple intracellular RNA sensing innate immune pathways have been linked to autoimmune disease. RNA-related ligands taken up by the endocytic pathway activate TLRs, and affect primarily immune cells. This type of activation is enhanced by nucleic acid-specific antibodies and induces an inflammatory program. In contrast, spontaneous activation of cytoplasmic RNA sensing pathways target mostly non-hematopoietic tissues and their effect on autoimmune disease is secondary to the release of interferon in the circulation. The fact that pathologies result from spontaneous activation of innate pathways implies that endogenous RNA ligands that might be sensed as pathogenic are commonly found in both immune and non-immune cells.
PMCID: PMC4100591  PMID: 24455767
25.  Beyond the transcriptome: Completion of Act One of the Immunological Genome Project 
Current opinion in immunology  2013;25(5):10.1016/j.coi.2013.09.013.
The Immunological Genome Consortium has generated a public resource ( that provides a compendium of gene expression profiles of ~270 leukocyte subsets in the mouse. This effort established carefully standardized operating procedures that resulted in a transcriptional dataset of unprecedented comprehensiveness and quality. The findings have been detailed recently in a series of publications providing molecular insights into the development, heterogeneity, and/or function of these cellular lineages and distinct subpopulations. Here, we review the key findings of these studies, highlighting what has been gained and how the knowledge can be used to accelerate progress toward a comprehensive understanding of the immune system.
PMCID: PMC3855358  PMID: 24168965

Results 1-25 (358)