The unique neonatal NK cells: a critical component required for neonatal autoimmune disease induction by maternal autoantibody
Human maternal autoantibodies can trigger autoimmune diseases such as congenital heart block (CHB) in the progeny of women with lupus or Sjogren's disease. The pathogenic effect of early autoantibody (autoAb) exposure has been investigated in a murine neonatal autoimmune ovarian disease (nAOD)...
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Published in | Frontiers in immunology Vol. 5; p. 242 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
28.05.2014
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Subjects | |
Online Access | Get full text |
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Summary: | Human maternal autoantibodies can trigger autoimmune diseases such as congenital heart block (CHB) in the progeny of women with lupus or Sjogren's disease. The pathogenic effect of early autoantibody (autoAb) exposure has been investigated in a murine neonatal autoimmune ovarian disease (nAOD) model triggered by a unique ZP3 antibody. Although immune complexes (IC) are formed in adult and neonatal ovaries, ZP3 antibody triggers severe nAOD only in <7-day-old neonatal mice. Propensity to nAOD is due to the uniquely hyper-responsive neonatal natural killer (NK) cells that lack the inhibitory Ly49C/I receptors. In nAOD, the neonatal NK cells directly mediate ovarian inflammation and oocyte depletion while simultaneously promoting de novo pathogenic ovarian-specific T cell responses. Resistance to nAOD in older mice results from the emergence of the Ly49C/I(+) NK cells that regulate effector NK cells and from CD25(+) regulatory T cell control. In preliminary studies, FcγRIII(+) NK cells as well as the ovarian resident FcγRIII(+) macrophages and/or dendritic cells were found to be as indispensable players. Activated by ovarian IC, they migrate to lymphoid organs where NK cell priming occurs. Remarkably, the findings in nAOD are very similar to those reported for neonatal responses to a retrovirus and its cognate antibody that lead to long-lasting immunity. Studies on nAOD therefore provide insights into maternal autoAb-mediated neonatal autoimmunity, including CHB, while simultaneously uncovering new properties of the neonatal innate and adaptive responses, lethality of premature infant infection, and novel neonatal antiviral vaccine design. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 This article was submitted to Inflammation, a section of the journal Frontiers in Immunology. Edited by: Sinuhe Hahn, University Clinics Basel, Switzerland Reviewed by: Daisuke Kamimura, Osaka University, Japan; Ana Claudia Zenclussen, Otto-von-Guericke University, Germany |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2014.00242 |