Basement membranes and autoimmune diseases

Foster, Mary H.

doi:10.1016/j.matbio.2016.07.008

Cited by 38 publications

(25 citation statements)

References 214 publications

(195 reference statements)

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“…Basement membranes are chiefly composed of four requisite components: laminin [93], collagen IV [94], nidogen, and the heparan sulfate proteoglycan (HSPG) perlecan [95,96], The biology and contributions of collagen XVIII, a related basement HSPG implicated in tissue homeostasis and dysfunction, has been recently reviewed [97], Unbiased quantitative proteomic definitions of basement membrane compositions [98] and extracellular matrices [99,100] are leading an “-omics” revolution in understanding the functional contributions of basement membrane in associated diseases [101–103], development [104,105] and potentially as viable cell-based therapeutic modalities [106], Perlecan and related components [107] are critical for maintaining the structural integrity of cartilage and assembly of basement membrane [108], while maintaining sufficient plasticity for remodeling as the organism grows and develops over time. Indeed, embryo implantation triggers dynamic expression of the basement membrane toolkit [109].…”

Section: Concept Of Matrix Modeling and Remodelingmentioning

confidence: 99%

Matrix modeling and remodeling: A biological interplay regulating tissue homeostasis and diseases

et al. 2019

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The overall structure and architecture of the extracellular matrix undergo dramatic alterations in composition, form, and functionality over time. The stochasticity begins during development, essential for maintaining organismal homeostasis and is heavily implicated in many pathobiological states including fibrosis and cancer. Modeling and remodeling of the matrix is driven by the local cellular milieu and secreted and cell-associated components in a framework of dynamic reciprocity. This collection of expertly-written reviews aims to relay state-of-the-art information concerning the mechanisms of matrix modeling and remodeling in physiological development and disease.

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Section: Concept Of Matrix Modeling and Remodelingmentioning

confidence: 99%

Matrix modeling and remodeling: A biological interplay regulating tissue homeostasis and diseases

et al. 2019

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“…The IgMa Tg was originally constructed from the dominant Ig heavy chain of an IgG autoAb derived from a nephritic MRL/lpr mouse (28). The index IgG binds to laminin, a multifunctional glycoprotein expressed in basement membranes and a target of autoAbs implicated in SLE, blistering dermatoses, reproductive failure, and other disorders (29–34). A prominent subset of Tg autoAbs also crossreacts with DNA (28), a prototypical target antigen in SLE.…”

Section: Introductionmentioning

confidence: 99%

Silica Exposure Differentially Modulates Autoimmunity in Lupus Strains and Autoantibody Transgenic Mice

et al. 2019

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Inhalational exposure to crystalline silica is linked to several debilitating systemic autoimmune diseases characterized by a prominent humoral immune component, but the mechanisms by which silica induces autoantibodies is poorly understood. To better understand how silica lung exposure breaks B cell tolerance and unleashes autoreactive B cells, we exposed both wildtype mice of healthy C57BL/6 and lupus-prone BXSB, MRL, and NZB strains and mice carrying an autoantibody transgene on each of these backgrounds to instilled silica or vehicle and monitored lung injury, autoimmunity, and B cell fate. Silica exposure induced lung damage and pulmonary lymphoid aggregates in all strains, including in genetically diverse backgrounds and in autoantibody transgenic models. In wildtype mice strain differences were observed in specificity of autoantibodies and site of enhanced autoantibody production, consistent with genetic modulation of the autoimmune response to silica. The unique autoantibody transgene reporter system permitted the in vivo fate of autoreactive B cells and tolerance mechanisms to be tracked directly, and demonstrated the presence of transgenic B cells and antibody in pulmonary lymphoid aggregates and bronchoalveolar lavage fluid, respectively, as well as in spleen and serum. Nonetheless, B cell enumeration and transgenic antibody quantitation indicated that B cell deletion and anergy were intact in the different genetic backgrounds. Thus, silica exposure sufficient to induce substantial lung immunopathology did not overtly disrupt central B cell tolerance, even when superimposed on autoimmune genetic susceptibility. This suggests that silica exposure subverts tolerance at alternative checkpoints, such as regulatory cells or follicle entry, or requires additional interactions or co-exposures to induce loss of tolerance. This possibility is supported by results of differentiation assays that demonstrated transgenic autoantibodies in supernatants of Toll-like receptor (TLR)7/TLR9-stimulated splenocytes harvested from silica-exposed, but not vehicle-exposed, C57BL/6 mice. This suggests that lung injury induced by silica exposure has systemic effects that subtly alter autoreactive B cell regulation, possibly modulating B cell anergy, and that can be unmasked by superimposed exposure to TLR ligands or other immunostimulants.

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“…Collagen IV is a main constituent of all basement membranes, specialized form of extracellular matrix, which support tissue integrity and perform numerous key functions including cell signaling, morphogenesis, and tissue regeneration [17]. While Goodpasture’s disease has been long recognized as an autoimmune collagen IV disorder, other basement membrane components are also targeted by antibodies in several autoimmune diseases [18].…”

Section: Introductionmentioning

confidence: 99%

Goodpasture's autoimmune disease — A collagen IV disorder

2018

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Goodpasture's (GP) disease is an autoimmune disorder characterized by the deposition of pathogenic autoantibodies in basement membranes of kidney and lung eliciting rapidly progressive glomerulonephritis and pulmonary hemorrhage. The principal autoantigen is the α345 network of collagen IV, which expression is restricted to target tissues. Recent discoveries include a key role of chloride and bromide for network assembly, a novel posttranslational modification of the antigen, a sulfilimine bond that crosslinks the antigen, and the mechanistic role of HLA in genetic susceptibility and resistance to GP disease. These advances provide further insights into molecular mechanisms of initiation and progression of GP disease and serve as a basis for developing of novel diagnostic tools and therapies for treatment of Goodpasture's disease.

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Basement membranes and autoimmune diseases

Cited by 38 publications

References 214 publications

Matrix modeling and remodeling: A biological interplay regulating tissue homeostasis and diseases

Matrix modeling and remodeling: A biological interplay regulating tissue homeostasis and diseases

Silica Exposure Differentially Modulates Autoimmunity in Lupus Strains and Autoantibody Transgenic Mice

Goodpasture's autoimmune disease — A collagen IV disorder

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