Interleukin-4 (IL-4) is an endogenous inhibitor of neutrophil influx and subsequent glomerular pathology in acute antibody-mediated murine nephritis

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IL-4 is an endogenous inhibitor of neutrophil influx and subsequent pathology in acute antibody-mediated inflammation

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Interleukin-4 and interleukin-13 act on glomerular visceral epithelial cells

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Hydractinia allodeterminant alr1 resides in an immunoglobulin superfamily-like gene complex

Allorecognition, the ability to discriminate between self and nonself, is ubiquitous among colonial metazoans and widespread among aclonal taxa [1-3]. Genetic models for the study of allorecognition have been developed in the jawed vertebrates [4], invertebrate chordate Botryllus [5, 6], and cnidarian Hydractinia [7]. In Botryllus, two genes contribute to the histocompatibility response, FuHC [5, 8] and fester [6]. In the cnidarian Hydractinia, one of the two known allorecognition loci, alr2, has been isolated [7], and a second linked locus, alr1, has been mapped to the same chromosomal region, called the allorecognition complex (ARC) [9, 10]. Here we isolate alr1 by positional cloning and report it to encode a transmembrane receptor protein with two hypervariable extracellular regions similar to immunoglobulin (Ig)-like domains. Variation in the extracellular domain largely predicts fusibility within and between laboratory strains and wild-type isolates. alr1 was found embedded in a family of immunoglobulin superfamily (IgSF)-like genes, thus establishing that the ARC histocompatibility complex is an invertebrate IgSF-like gene complex. © 2010 Elsevier Ltd. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Hydractinia allodeterminant alr1 resides in an immunoglobulin superfamily-like gene complex

Allorecognition, the ability to discriminate between self and nonself, is ubiquitous among colonial metazoans and widespread among aclonal taxa [1-3]. Genetic models for the study of allorecognition have been developed in the jawed vertebrates [4], invertebrate chordate Botryllus [5, 6], and cnidarian Hydractinia [7]. In Botryllus, two genes contribute to the histocompatibility response, FuHC [5, 8] and fester [6]. In the cnidarian Hydractinia, one of the two known allorecognition loci, alr2, has been isolated [7], and a second linked locus, alr1, has been mapped to the same chromosomal region, called the allorecognition complex (ARC) [9, 10]. Here we isolate alr1 by positional cloning and report it to encode a transmembrane receptor protein with two hypervariable extracellular regions similar to immunoglobulin (Ig)-like domains. Variation in the extracellular domain largely predicts fusibility within and between laboratory strains and wild-type isolates. alr1 was found embedded in a family of immunoglobulin superfamily (IgSF)-like genes, thus establishing that the ARC histocompatibility complex is an invertebrate IgSF-like gene complex. © 2010 Elsevier Ltd. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Failure to induce anti-glomerular basement membrane glomerulonephritis in TNFα/β deficient mice

TNF is a key proinflammatory cytokine playing a central role in the expression of endothelial adhesion molecules required for the recruitment of inflammatory cells. Proliferative glomerulonephritis induced by anti-GBM antibody is characterized by the recruitment of inflammatory cells into the glomerulus and capillary damage followed by regeneration with crescent formation. The glomerular pathology may be due to TNF induction and we therefore tested this hypothesis in TNFα/β deficient mice. Anti-GBM antibody administration in sensitised wild-type mice resulted in deposition of immune complexes and complement factor 3, followed by increased ICAM-1 and VCAM-1 expression and influx of polymorphonucelar leucocytes. Distinct proteinuria precedes proliferative glomerulonephritis with glomerular crescent formation, which is fully developed at 10 days. By contrast, no glomerulonephritis developed in TNFα/β deficient mice. Comparable antibody complex deposits are found, but the upregulation of ICAM-1 and VCAM-1, the influx of inflammatory cells and the subsequent tissue damage is absent in TNFα/β deficient mice. Therefore, we conclude that TNF plays a key role for the recruitment of inflammatory cells by preventing the upregulation of endothelial adhesion molecule and the subsequent development of proliferative glomerulonephritis