2016
DOI: 10.4049/jimmunol.1502539
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Lung Injury Combined with Loss of Regulatory T Cells Leads to De Novo Lung-Restricted Autoimmunity

Abstract: Over one-third of patients with chronic lung disease undergoing lung transplantation have pre-existing antibodies against lung-restricted self-antigens, collagen type V (ColV) and k-alpha1 tubulin (KAT). These antibodies can also develop de novo following lung transplantation and mediate allograft rejection. However, the mechanisms leading to lung-restricted autoimmunity remain unknown. Since these self-antigens are normally sequestered, tissue injury is required to expose them to the immune system. We previou… Show more

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Cited by 25 publications
(30 citation statements)
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“…86 Infection is perhaps the best example of a non-specific inflammatory response that can ultimately result in alloimmunity. 86 Infection is perhaps the best example of a non-specific inflammatory response that can ultimately result in alloimmunity.…”
Section: Barriers To Tolerance In Lung Transplantationmentioning
confidence: 99%
See 1 more Smart Citation
“…86 Infection is perhaps the best example of a non-specific inflammatory response that can ultimately result in alloimmunity. 86 Infection is perhaps the best example of a non-specific inflammatory response that can ultimately result in alloimmunity.…”
Section: Barriers To Tolerance In Lung Transplantationmentioning
confidence: 99%
“…Their work suggested that Treg loss, which can be triggered by respiratory viruses, in combination with ongoing graft injury caused by either gastroesophageal reflux or donor-specific antibodies, trigger lung-restricted immune responses. 86 Infection is perhaps the best example of a non-specific inflammatory response that can ultimately result in alloimmunity. In 2007, our laboratory was the first to establish an orthotopic, vascularized mouse lung transplant model.…”
Section: Barriers To Tolerance In Lung Transplantationmentioning
confidence: 99%
“…It is of interest that viruses are often associated with a variety of autoimmune diseases [24, 44]. In this context, we demonstrated that LTx recipients who develop respiratory viral infections demonstrate a transient loss of Tregs [42, 45]. Interestingly, if these recipients had a preexisting lung injury mechanism (e.g., donor-specific HLA Abs or gastroesophageal reflux), they are at increased risk of developing de novo lung-restricted autoimmunity.…”
Section: Pathogenesis Of Lung-restricted Autoimmunity (Lra)mentioning
confidence: 99%
“…We therefore tested whether lung injury and concomitant loss of Tregs in wild-type hosts would lead to LRA. Immunocompetent mice were injected with either hydrochloric acid or Abs to MHC class I, and Tregs were depleted by either murine parainfluenza Sendai virus (in wild-type mice) or diphtheria toxin (in Foxp3-DTR mice) [45]. This resulted in the development of both cellular and humoral immunity against lung-restricted SAgs.…”
Section: Pathogenesis Of Lung-restricted Autoimmunity (Lra)mentioning
confidence: 99%
“…The release of IL-1α from dying AMs following crystalline particle inhalation is unique because other macrophage populations do not release IL-1α without a priming TLR signal (1,12). Inhalation of fine particles can drive acute pulmonary inflammation, enhance adaptive immune responses to bystander or self-antigens, and increase the risk for developing allergy and certain types of autoimmune disease (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Chronic beryllium disease (CBD) is both a metal-induced hypersensitivity and autoimmune disease to self-peptides (24).…”
Section: Introductionmentioning
confidence: 99%