Interaction between ANXA1 and GATA-3 in Immunosuppression of CD4⁺ T Cells

Abstract

Decreased Th1/Th2 ratio is one of the major characteristics of immunosuppression in sepsis. Both membrane adhesive protein Annexin-A1 (ANXA1) and transcription factor GATA-3 have been reported to play important roles in T cell differentiation. However, the relationship between ANXA1 and GATA-3 in Th1/Th2 shift is unknown. Our study investigated the interaction effects of ANXA1 and GATA-3 to influence T cell differentiation in CD4+ T cells. We found that GATA-3 and ANXA1 were coexpressed on Th0/Th1/Th2 cytoplasm and nuclear. Overexpressed ANXA1 significantly increased the expression of IFNγ and reduced IL-4 expression in T cells, while ANXA1-silenced T cells exhibited decreased production of IFNγ and increased production of IL-4. Knockdown of ANXA1 promoted higher expression level of GATA-3 and low level of T-box transcription factor (T-bet/Tbx21). Further study demonstrated that ANXA1 regulated GATA-3 expression through the formyl peptide receptor like-1 (FPRL-1) downstream signaling pathways ERK and PKB/Akt. These results suggested that ANXA1 modulates GATA-3/T-bet expression induced Th0/Th1 differentiation. Moreover, we found that GATA-3 inhibited ANXA1 expression by binding to its promoter for the first time. It is proposed that the interactions between ANXA1 and GATA-3 may provide clues to understand the immunosuppression and have potential as new therapeutic targets in immunotherapy after sepsis.

Annexin A1 down-regulation in head and neck squamous cell carcinoma is mediated via transcriptional control with direct involvement of miR-196a/b

“…miR-196b is a post-transcriptional inhibitor of the GATA transcription factor 27 , which interacts with ANXA1 28 possibly by binding to its promoter (see Fig. 6a).…”

Schistosomal extracellular vesicle‐enclosed miRNAs modulate host T helper cell differentiation

“…For example, Anxa1, whose overexpression reduces GATA3 and increases T-bet levels [43], was increased by 1.86-fold. For example, Anxa1, whose overexpression reduces GATA3 and increases T-bet levels [43], was increased by 1.86-fold.…”

Dying to Be Noticed: Epigenetic Regulation of Immunogenic Cell Death for Cancer Immunotherapy

“…Annexin A1, known for its immunosuppressive functions ( 81 ), has recently been found to contribute to DC function during ICD. Here, ANXA1 released from the apoptotic cells can bind to formyl peptide receptor 1 receptor on APCs, enabling the stable interaction between the APC and dying cancer cell ( 82 – 84 ).…”