Abstract：
:The discovery of the autoimmune regulator (AIRE) protein and the delineation of its critical contributions in the establishment of central immune tolerance has significantly expanded our understanding of the immunological mechanisms that protect from the development of autoimmune disease. The parallel identification and characterization of patient cohorts with the monogenic disorder autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), which is typically caused by biallelic AIRE mutations, has underscored the critical contribution of AIRE in fungal immune surveillance at mucosal surfaces and in prevention of multiorgan autoimmunity in humans. In this review, we synthesize the current clinical, genetic, molecular and immunological knowledge derived from basic studies in Aire-deficient animals and from APECED patient cohorts. We also outline major advances and research endeavors that show promise for informing improved diagnostic and therapeutic approaches for patients with APECED.
journal_name
Immunol Revjournal_title
Immunological reviewsauthors
Constantine GM,Lionakis MSdoi
10.1111/imr.12714subject
Has Abstractpub_date
2019-01-01 00:00:00pages
103-120issue
1eissn
0105-2896issn
1600-065Xjournal_volume
287pub_type
杂志文章,评审abstract：:The genes that encode molecules involved in antigen presentation within the class I and class II regions of the mammalian major histocompatibility complex (MHC) include several that are highly polymorphic. There is evidence that this polymorphism is maintained by positive selection, most likely overdominant selection,...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1999.tb01381.x
更新日期：1999-02-01 00:00:00
abstract：:Immunologists working in the field of autoimmunity tend to concentrate all their efforts on the elucidation of possible malfunctions of the immune system, particularly pathologic changes of immune regulation. Also in the OS model various groups of investigators emphasized this approach, although it was already clear e...
journal_title：Immunological reviews
pub_type： 杂志文章
doi：10.1111/j.1600-065x.1986.tb01167.x
更新日期：1986-12-01 00:00:00
abstract：:The surface molecules that mediate activation of different subsets of T or NK cells have been reviewed. A suitable approach to the study of different lymphocyte activation pathways is provided by mAbs specific for these molecules. MAbs directed to the CD3 surface molecules mediate a polyclonal T-cell activation, where...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1989.tb00545.x
更新日期：1989-10-01 00:00:00
abstract：:As biomedical research becomes increasingly data-intensive, it is increasingly essential to integrate genomic-scale datasets, so as to generate a more holistic picture of complex biological processes. The systems biology paradigm may differ in strategy from traditional reductionist scientific methods, but the goal rem...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2010.00998.x
更新日期：2011-03-01 00:00:00
abstract：:Newfound relatives of the classical Fc receptors (FcR) have been provisionally named the Fc receptor homologs (FcRH). The recent identification of eight human and six mouse FcRH genes substantially increases the size and functional potential of the FcR family. The extended family of FcR and FcRH genes spans approximat...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2002.19009.x
更新日期：2002-12-01 00:00:00
abstract：:Structures of two intact monoclonal antibodies were solved by X-ray diffraction analysis revealing, in both cases, the dispositions of all segments, as well as the structures of the hinge polypeptides. An IgG1, whose antigen is the drug phenobarbital, assumed a completely different conformation when compared with an I...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01186.x
更新日期：1998-06-01 00:00:00
abstract：SUMMARY:Dengue viruses (DENV) are the mosquito-borne viruses of greatest global public health importance. DENV circulate as four serotypes with significant immunologic cross-reactivity that does not provide protection from secondary infection with heterologous serotypes. The strong association of severe dengue illness,...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2008.00678.x
更新日期：2008-10-01 00:00:00
abstract：:Once across the barrier of the epithelium, macrophages constitute the primary defense against microbial invasion. For most microbes, the acidic, hydrolytically competent environment of the phagolysosome is sufficient to kill them. Despite our understanding of the trafficking events that regulate phagosome maturation, ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2007.00547.x
更新日期：2007-10-01 00:00:00
abstract：:Ubiquitination is a post-translational modification process that regulates several critical cellular processes. Ubiquitination is orchestrated by the ubiquitin proteasome system (UPS), which constitutes a cascade of enzymes that transfer ubiquitin onto protein substrates. The UPS catalyzes the destruction of many crit...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12236
更新日期：2015-01-01 00:00:00
abstract：:Shc is a prototype adapter protein that is expressed from the earliest stages of T-cell development. Shc becomes rapidly tyrosine phosphorylated after T-cell receptor (TCR) engagement. Expression of dominant negative forms of Shc in T-cell lines had also suggested a role for this adapter downstream of the TCR. However...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2003.00025.x
更新日期：2003-02-01 00:00:00
abstract：:The immunoglobulin heavy chain locus in teleost fish is structurally similar to that in mammals, comprising a series of variable gene segments upstream of two constant region genes coding for IgM and IgD. Atlantic salmon have been shown to possess two distinct heavy chain loci, related to the tetraploid ancestry of th...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01260.x
更新日期：1998-12-01 00:00:00
abstract：:Antiretroviral therapy (ART) is a life-saving intervention in human immunodeficiency virus (HIV) infection. Immune restoration after ART dramatically reduces the incidence and severity of opportunistic diseases and death. On some occasions, immune restoration may be erratic, leading to acute inflammatory responses (kn...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12064
更新日期：2013-07-01 00:00:00
abstract：:In the human, most IgM+IgD+ as well as CD5+ peripheral blood B cells express unmutated V genes and thus can be assigned to a pre-germinal centre (GC) stage of development. The memory B-cell compartment generated in the GC reaction and characterized by cells bearing somatically mutated V-region genes consists not only ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01447.x
更新日期：1998-04-01 00:00:00
abstract：:Lymphocytes can interfere with the activity of other lymphocytes in a thousand and one ways. A particular subset of so-called regulatory CD4+ T cells is capable of controlling the activity of other lymphocytes in yet another way. Their function is primarily defined by the ability to protect the integrity of tissues an...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2001.1820101.x
更新日期：2001-08-01 00:00:00
abstract：:The immature and transitional immature B-cell stages define an important window in B-cell development, as it is at this point that cells committed to the B-cell lineage first express the clonotypic B-cell antigen receptor (BCR) and cells expressing self-reactive specificities may be identified and eliminated. The intr...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2000.00609.x
更新日期：2000-08-01 00:00:00
abstract：:The recurrence in the V-gene repertoire of individual germline VH genes can now be extended from the restricted B-cell populations of the fetus, autoantibodies and B-cell malignancies to the expressed V-gene repertoire of normal adults. Why the human B cell preferentially utilizes these individual VH genes remains spe...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1992.tb00834.x
更新日期：1992-08-01 00:00:00
abstract：:Resistance to infection with Listeria monocytogenes involves a series of cellular interactions, many of which are carried out by cytokines. Macrophages, NK cells and neutrophils participate in early stages of Listeria resistance. The neutrophil is specially important for clearance of the liver phase of listeriosis. Ma...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1997.tb00988.x
更新日期：1997-08-01 00:00:00
abstract：:The gammadelta T-cell receptors (TCRs) are limited in their diversity, suggesting that their natural ligands may be few in number. Ligands for gammadeltaTCRs that have thus far been determined are predominantly of host rather than foreign origin. Correlations have been noted between the Vgamma and/or Vdelta genes a ga...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2006.00477.x
更新日期：2007-02-01 00:00:00
abstract：:A key unresolved challenge for developing an effective HIV-1 vaccine is the discovery of strategies to elicit immune responses that are able to cross-protect against a significant fraction of the diverse viruses that are circulating worldwide. Here, we summarize some of the immunological implications of HIV-1 diversit...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12516
更新日期：2017-01-01 00:00:00
abstract：SUMMARY:This volume covers many topics in the field of T-cell costimulation. The need for such a volume is testament to the growth of the field. From its beginning as a concept in the 1980s, we have now progressed to the point where many molecules now have functionally defined roles in T-cell costimulation. In addition...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2009.00780.x
更新日期：2009-05-01 00:00:00
abstract：:Interleukin-12 (IL-12) and IL-23 share a common chain. Yet, their production in response to pathogens is differentially regulated, and their functions are distinct and often antithetic. IL-12 is involved in the induction or amplification of the T-helper (Th) type 1 response, whereas IL-23 has been associated with the ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2008.00700.x
更新日期：2008-12-01 00:00:00
abstract：:The sequence analysis of Ig variable region genes transcribed within different B-cell subpopulations from human tonsil led us to identify a rare DNA sequence modification event consisting of bp insertions and/or deletions (I/D). Although these events were previously reported, they had never been formally associated wi...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01437.x
更新日期：1998-04-01 00:00:00
abstract：:Multiple sclerosis is believed to be mediated by T cells specific for myelin antigens that circulate harmlessly in the periphery of healthy individuals until they are erroneously activated by an environmental stimulus. Upon activation, the T cells enter the central nervous system and orchestrate an immune response aga...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2011.01016.x
更新日期：2011-05-01 00:00:00
abstract：:Because of its intrinsic virulence, Toxoplasma gondii induces a potent interleukin-12 (IL-12)-dependent cell-mediated immune response that shuts down the growth of the replicative tachyzoite stage, thus promoting host survival and successful transmission through predation. At the same time, this response must be tight...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2004.00179.x
更新日期：2004-10-01 00:00:00
abstract：:X-linked lymphoproliferative disease (XLP) is an inherited immune defect caused by mutations in the Src homology 2 domain-containing gene 1A, which encodes the adapter protein, signaling lymphocytic activation molecule (SLAM)-associated protein (SAP). SAP is expressed in T cells, natural killer (NK) cells, and NKT cel...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2005.00230.x
更新日期：2005-02-01 00:00:00
abstract：:The innate immune system is responsible for detecting microbial invasion of the cell and for stimulating host defense countermeasures. These anti-pathogen procedures include the transcriptional activation of powerful antiviral genes such as the type I interferons (IFNs) or the triggering of inflammatory responses thro...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2011.01051.x
更新日期：2011-09-01 00:00:00
abstract：:Fcγ receptors (FcγRs) are key immune receptors responsible for the effective control of both humoral and innate immunity and are central to maintaining the balance between generating appropriate responses to infection and preventing autoimmunity. When this balance is lost, pathology results in increased susceptibility...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12341
更新日期：2015-11-01 00:00:00
abstract：:The scale and scope of the global epidemic, coupled to challenges with traditional vaccine development approaches, point toward a need for novel methodologies for HIV vaccine research. While the development of vaccines able to induce broadly neutralizing antibodies remains the ultimate goal, to date, vaccines continue...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12503
更新日期：2017-01-01 00:00:00
abstract：:The bronchus-associated lymphoid tissue (BALT) and the nasal-associated lymphoid tissue (NALT) constitute organized lymphoid aggregates that are capable of T- and B-cell responses to inhaled antigens. BALT, located mostly at bifurcations of the bronchus in animals and humans, is present in the fetus and develops rapid...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2005.00299.x
更新日期：2005-08-01 00:00:00
abstract：:For more than 25 years, it has been widely appreciated that Ca2+ influx is essential to trigger T-lymphocyte activation. Patch clamp analysis, molecular identification, and functional studies using blockers and genetic manipulation have shown that a unique contingent of ion channels orchestrates the initiation, intens...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2009.00816.x
更新日期：2009-09-01 00:00:00
