Interleukin‐21 suppresses the differentiation and functions of T helper 2 cells

T helper type 2 (Th2) cells, which produce interleukin‐4 (IL‐4), IL‐5 and IL‐13, control immunity to all forms of allergic inflammatory responses. Interleukin‐21 (IL‐21) reduces allergic symptoms in murine models and inhibits IL‐4‐induced IgE secretion by B cells. However, whether or not IL‐21 directly affects Th2 cells, which leads to reduced allergic symptoms, is unclear. In this study, we investigated the effects of IL‐21 on the differentiation and effector functions of Th2 cells. We found that IL‐21 reduced the number of differentiated Th2 cells and these Th2 cells showed a diminished Th2 cytokine production. Interleukin‐21 suppressed Th2 cytokine production of already polarized Th2 cells by down‐regulation of transcription factor GATA‐3. It also induced apoptosis of Th2 cells with decreased anti‐apoptotic factor Bcl‐2. Intranasal administration of IL‐21 at the beginning of ovalbumin (OVA) sensitization or before OVA challenge decreased Th2 cytokines in the bronchoalveolar lavage fluid of OVA/alum‐immunized allergic mice. In addition, the inhibitory effects of IL‐21 on Th2 effector functions can also be found in allergic patients. Our results demonstrate that IL‐21 suppresses the development of Th2 cells and functions of polarized Th2 cells. Hence, the administration of IL‐21 may be considered for use as a preventive and therapeutic approach when dealing with Th2‐mediated allergic diseases.

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