Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Blockade of STAT3 in T Cells Inhibits Germinal Center Reactions against Intranasal Allergens

  • Choi, Garam (Laboratory of Immune Regulation, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University) ;
  • Chung, Yeonseok (Laboratory of Immune Regulation, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University)
  • Received : 2015.09.25
  • Accepted : 2015.10.21
  • Published : 2016.05.01
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Abstract

Understanding the developmental mechanisms of humoral immunity against intranasal antigens is essential for the development of therapeutic approaches against air-borne pathogens as well as allergen-induced pulmonary inflammation. Follicular helper T (Tfh) cells expressing CXCR5 are required for humoral immunity by providing IL-21 and ICOS costimulation to activated B cells. However, the regulation of Tfh cell responses against intranasal antigens remains unclear. Here, we found that the generation of Tfh cells and germinal center B cells in the bronchial lymph node against intranasal proteinase antigens was independent of $TGF-{\beta}$. In contrast, administration of STAT3 inhibitor STA-21 suppressed the generation of Tfh cells and germinal center B cells. Compared with wild-type OT-II T cells, STAT3-deficient OT-II T cells transferred into recipients lacking T cells not only showed significantly reduced frequency Tfh cells, but also induced diminished IgG as well as IgE specific for the intranasal antigens. Cotransfer study of wild-type OT-II and STAT3-deficient OT-II T cells revealed that the latter failed to differentiate into Tfh cells. These findings demonstrate that T cell-intrinsic STAT3 is required for the generation of Tfh cells to intranasal antigens and that targeting STAT3 might be an effective approach to ameliorate antibody-mediated pathology in the lung.

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References

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