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Interleukin-2/antibody complex expanding Foxp3+ regulatory T cells exacerbates Th2-mediated allergic airway inflammation
Sung-wook Hong1,#, Eunju O1,2,#, Jun Young Lee1,2, Jaeu Yi1,2, Kyungjin Cho1,2, Juhee Kim1,2, Daeun Kim1,2, Charles D Surh1,2, Kwang Soon Kim1,2,*, Kwang Soon Kim1,2,*
1Academy of Immunology and Microbiology, Institute for Basic Science,
2Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH)
Abstract
Foxp3+ regulatory CD4+ T (Treg) cells play an essential role in preventing overt immune responses against self and innocuous foreign antigens. Selective expansion of endogenous Treg cells in response to the administration of interleukin (IL)-2/antibody complex, such as the IL-2/JES6-1 complex (IL-2C) in mice, is considered an attractive therapeutic approach to various immune disorders. Here, we investigated the therapeutic potential of IL-2C in allergic airway inflammation models. IL-2C treatment ameliorated Th17-mediated airway inflammation; however, unexpectedly, IL-2C treatment exacerbated Th2-mediated allergic airway inflammation by inducing the selective expansion of Th2 cells and type-2 innate lymphoid cells. We also found that IL-2 signaling is required for the expansion of Th2 cells in lymphoproliferative disease caused by Treg cell depletion. Our data suggest that IL-2C is selectively applicable to the treatment of allergic airway diseases depending on the characteristics of airway inflammation.
Abstract, Accepted Manuscript(in press) [Submitted on November 26, 2018, Accepted on March 12, 2019]
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