New Immune Mechanism – Implications for Autism ?

Scientists discover new mechanism regulating the immune response

http://www.alphagalileo.org/ViewItem.aspx?ItemId=132475&CultureCode=en

28 June 2013 Suomen Akatemia (Academy of Finland)

Scientists at an Academy of Finland Centre of Excellence have discovered a new mechanism regulating the immune response that can leave a person susceptible to autoimmune diseases.

A fresh study by Turku Centre for Biotechnology and Aalto University in Finland is the first to report a new mechanism that regulates specification of lymphocytes, the white blood cells pivotal to immune response.

By combining state-of-the art techniques, next-generation deep sequencing and computational data mining, the researchers discovered new epigenetic factors regulating lymphocyte function. Regulatory regions of the genes studied displayed variations (single nucleotide polymorphisms or SNPs) that have been associated with predisposition to autoimmune diseases such as type1 diabetes, rheumatoid arthritis and inflammatory bowel disease. These discoveries provide new insight into and basis for the study of emergent mechanisms of immune-mediated diseases.

Immune-mediated diseases such as type 1 diabetes, rheumatoid arthritis, asthma and allergies result from abnormal immune response. T lymphocytes that orchestrate the immune response can differentiate into functionally distinct lineages to combat infection and disease. The correct response to cytokines and a controlled balance of T lymphocyte populations are critical for the immune system and for the avoidance of autoimmune disorders.

http://dx.doi.org/10.1016/j.immuni.2013.05.011

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Global Chromatin State Analysis Reveals Lineage-Specific Enhancers during the Initiation of Human T helper 1 and T helper 2 Cell Polarization

 http://www.cell.com/immunity/retrieve/pii/S1074761313002379

  • Highlights
  • The first genome-wide maps of enhancer elements used in early Th1 and Th2 cell-lineage commitment
  • Lineage-specific enhancers are mapped to nucleosome-free resolution
  • Enhancers overlap SNPs associated with autoimmune disorders
  • SNPs often occur at enhancers within TF binding-site motifs

Summary

Naive CD4+ T cells can differentiate into specific helper and regulatory T cell lineages in order to combat infection and disease.

The correct response to cytokines and a controlled balance of these populations is critical for the immune system and the avoidance of autoimmune disorders.

To investigate how early cell-fate commitment is regulated, we generated the first human genome-wide maps of histone modifications that reveal enhancer elements after 72 hr of in vitro polarization toward T helper 1 (Th1) and T helper 2 (Th2) cell lineages.

Our analysis indicated that even at this very early time point, cell-specific gene regulation and enhancers were at work directing lineage commitment. Further examination of lineage-specific enhancers identified transcription factors (TFs) with known and unknown T cell roles as putative drivers of lineage-specific gene expression.

Lastly, an integrative analysis of immunopathogenic-associated SNPs suggests a role for distal regulatory elements in disease etiology.

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This entry was posted in Allergy, Asthma, Autism, co-morbid, diabetes, Environment, Epigenetics, Immune System, Inflammation. Bookmark the permalink.

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