Seminars in arthritis and rheumatism · 2008
Thymic Hassall's corpuscles, regulatory T-cells, and rheumatoid arthritis.
СтатьяОбзорНазвание и аннотация: Перевод в очереди
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Berthelot Jean-Marie, le Goff Benoît, Maugars Yves
Аннотация
OBJECTIVE: To review evidence for the involvement of thymic Hassall's corpuscles (HC) in the pathogenesis of rheumatoid arthritis (RA).
METHODS: We used PubMed to search for articles dedicated to the involvement of HC and regulatory T-cells (Tregs) in the pathogenesis of RA, and articles on thymic B-cells.
RESULTS: Tregs are central players mediating tolerance to self. The functional defects in Tregs observed in patients with active RA may contribute to RA pathogenesis, promoting the premature immunosenescence of T-cells. This may partly explain the persisting expansion of CD4+ effector T-cell clones in peripheral blood, as well as the parallel improvement of RA activity and numbers of Tregs observed in the third trimester of pregnancy. HC play a major role in the selection of natural Tregs in the thymus, potentially altering the peripheral Tregs repertoire. The promiscuous expression of tissue-specific antigens by thymic medullary epithelial cells shapes the repertoire of natural Tregs. Thus, the presence of 2 major RA autoantigens (immunoglobulins and filaggrin) in the cytoplasm of normal human HC is puzzling, particularly given that thymic B-cells are also concentrated around HC, where CD55 (DAF) and CD59 are strongly expressed. Defects in HC could alter the repertoire of thymic B-cells and Tregs in RA patients, promoting the onset of this disorder.
CONCLUSION: The identification of other joint-specific antigens, like gp-39, in HC and medullary epithelial cells, would provide new insights into the mechanisms of RA pathogenesis and may lead to more specific and physiologic methods of immunomodulation.
METHODS: We used PubMed to search for articles dedicated to the involvement of HC and regulatory T-cells (Tregs) in the pathogenesis of RA, and articles on thymic B-cells.
RESULTS: Tregs are central players mediating tolerance to self. The functional defects in Tregs observed in patients with active RA may contribute to RA pathogenesis, promoting the premature immunosenescence of T-cells. This may partly explain the persisting expansion of CD4+ effector T-cell clones in peripheral blood, as well as the parallel improvement of RA activity and numbers of Tregs observed in the third trimester of pregnancy. HC play a major role in the selection of natural Tregs in the thymus, potentially altering the peripheral Tregs repertoire. The promiscuous expression of tissue-specific antigens by thymic medullary epithelial cells shapes the repertoire of natural Tregs. Thus, the presence of 2 major RA autoantigens (immunoglobulins and filaggrin) in the cytoplasm of normal human HC is puzzling, particularly given that thymic B-cells are also concentrated around HC, where CD55 (DAF) and CD59 are strongly expressed. Defects in HC could alter the repertoire of thymic B-cells and Tregs in RA patients, promoting the onset of this disorder.
CONCLUSION: The identification of other joint-specific antigens, like gp-39, in HC and medullary epithelial cells, would provide new insights into the mechanisms of RA pathogenesis and may lead to more specific and physiologic methods of immunomodulation.