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. 2021 Apr 27;12:667342. doi: 10.3389/fimmu.2021.667342

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Copyright © 2021 Papillion and Ballesteros-Tato

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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IL-6 mediates the IL-2 responsiveness of Tfh cells. In the presence of IL-6 signaling, Tfh cells activate STAT3 which directly binds to the Il2rb promoter preventing expression of CD122. Low expression of CD122 limits IL-2 signaling in Tfh cells. In the absence of IL-6 signaling, there is increased expression of CD122 on the surface of Tfh cells leading to increased responsiveness to IL-2. The increased IL-2 signaling activates STAT5 which binds to the promoter region of Bcl6 and suppresses the Tfh cell program.