Biomol Ther.  2016 May;24(3):244-251. 10.4062/biomolther.2015.160.

Blockade of STAT3 in T Cells Inhibits Germinal Center Reactions against Intranasal Allergens

• Choi G
• Chung Y

• KMID: 2164216
• DOI: http://doi.org/10.4062/biomolther.2015.160

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-β. 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. Co-transfer 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.

Keyword

STAT3; Intranasal allergens; Tfh cell; Germinal center reactions; Immunoglobulin

MeSH Terms

Allergens*
B-Lymphocytes
Germinal Center*
Immunity, Humoral
Immunoglobulin E
Immunoglobulin G
Immunoglobulins
Lung
Lymph Nodes
Pathology
Pneumonia
T-Lymphocytes*
Allergens
Immunoglobulin E
Immunoglobulin G
Immunoglobulins