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Epigenetics, autoimmunity and hematologic malignancies: A comprehensive review

Journal

JOURNAL OF AUTOIMMUNITY
Volume 39, Issue 4, Pages 451-465

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2012.09.002

Keywords

Autoimmune disease; Hematological malignancy; Treg cells; Th17 cells; Epigenetics

Categories

Funding

  1. National Natural Science Foundation of China [30730083, 81101194, 30901300]
  2. National Basic Research Program of China (973 Plan) [2009CB825605]

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The relationships between immunological dysfunction, loss of tolerance and hematologic malignancies have been a focus of attention in attempts to understand the appearance of a higher degree of autoimmune disease and lymphoma in children with congenital immunodeficiency. Although multiple hypotheses have been offered, it is clear that stochastic processes play an important role in the immunopathology of these issues. In particular, accumulating evidence is defining a role of epigenetic mechanisms as being critical in this continuous spectrum between autoimmunity and lymphoma. In this review, we focus attention predominantly on the relationships between T helper 17 (Th17) and T regulatory populations that alter local microenvironments and ultimately the expression or transcription factors involved in cell activation and differentiation. Abnormal expression in any of the molecules involved in Th17 and/or Treg development alter immune homeostasis and in genetically susceptible hosts may lead to the appearance of autoimmunity and/or lymphoma. These observations have clinical significance in explaining the discordance of autoimmunity in identical twins. They are also particularly important in the relationships between primary immune deficiency syndromes, immune dysregulation and an increased risk of lymphoma. Indeed, defining the factors that determine epigenetic alterations and their relationships to immune homeostasis will be a challenge greater or even equal to the human genome project. (C) 2012 Elsevier Ltd. All rights reserved.

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