Interaction between ANXA1 and GATA-3 in Immunosuppression of CD4+T Cells.
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 IFNγand reduced IL-4 expression in T cells, while ANXA1-silenced T cells exhibited decreased production of IFNγand 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.
Department of Burns and Reconstructive Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Peng
P
Huang
Department of Burns and Reconstructive Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yuxiang
Y
Zhou
Department of Burns and Reconstructive Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zan
Z
Liu
Department of Burns and Reconstructive Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Pihong
0000-0003-0911-148X
P
Zhang
D000818:Animals; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D007165:Immunosuppression Therapy; D008297:Male; D051379:Mice; D011485:Protein Binding; D060888:Real-Time Polymerase Chain Reaction; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014162:Transfection
D017305:Annexin A1; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D044042:Receptors, Formyl Peptide; C573274:annexin A1, mouse; C481578:formyl peptide receptor 2, mouse