PMID- 29601942 OWN - NLM STAT- MEDLINE DCOM- 20190503 LR - 20190503 IS - 1879-0542 (Electronic) IS - 0165-2478 (Linking) VI - 198 DP - 2018 Jun TI - Effects of Toll-like receptor 4 on beta2-glycoprotein I-induced splenic T cell subsets differentiation. PG - 17-25 LID - S0165-2478(17)30408-X [pii] LID - 10.1016/j.imlet.2018.03.010 [doi] AB - Our previous study demonstrated that beta 2-glycoprotein I (beta2GPI) stimulation promotes bone marrow derived dendritic cells (BMDCs) maturation and T cell proliferation in a Toll-like receptor 4 (TLR4) dependent manner. However, beta2GPI induced T cell differentiation and the role of TLR4 in this process have rarely been reported. In the present study, we focused on the differentiation of splenic T cells in beta2GPI immunized Balb/c, C3H/HeN and C3H/HeJ mice. According to our results, Th2 dominated differentiation was observed in beta2GPI immunized Balb/c and C3H/HeN mice than in those treated with normal saline (NS), namely the up-regulated levels of Th2 markers GATA3 and IL-4 (p < 0.05). Meanwhile, reduced Th1 markers T-bet and IFN-gamma, and Treg marker Foxp3 were observed in beta2GPI immunized mice (p < 0.05). C3H/HeJ mice have the same gene background with C3H/HeN mice except a functional mutant in TLR4 gene. However, the described Th2 differentiation was not detected in these TLR4 deficient mice, indicating the importance of TLR4 in immune response against beta2GPI. In addition, we found that beta2GPI-induced Th2 differentiation could be strengthened by cytokines secreted by dendritic cells (DCs) and DCs-T cells interaction. However, DCs-T cells contact was indispensable during this process because of its unique role in suppressing Th1 function. Furthermore, this Th2 biased differentiation pattern was more noticeable in mice received 4 times beta2GPI immunization than those received 2 times, suggesting the amplifying effects of anti-beta2GPI Ab on beta2GPI induced Th2 response. These findings may partly explain the immune imbalance in APS patient through the view angle of T cell differentiation and anti-beta2GPI antibody production. CI - Copyright (c) 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved. FAU - He, Chao AU - He C AD - Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. FAU - Zhang, Guiting AU - Zhang G AD - Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. FAU - Zhou, Hong AU - Zhou H AD - Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. Electronic address: hongzhou@ujs.edu.cn. FAU - Cheng, Si AU - Cheng S AD - Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. FAU - Farwa, Amel AU - Farwa A AD - Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180327 PL - Netherlands TA - Immunol Lett JT - Immunology letters JID - 7910006 RN - 0 (Antibodies, Antiphospholipid) RN - 0 (Cytokines) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 4) RN - 0 (beta 2-Glycoprotein I) SB - IM MH - Animals MH - Antibodies, Antiphospholipid/immunology MH - Antigen Presentation MH - Cell Differentiation/*immunology MH - Cytokines/metabolism MH - Dendritic Cells/immunology/metabolism MH - Immunization MH - Lymphocyte Activation MH - Male MH - Mice MH - Spleen/*immunology MH - T-Lymphocyte Subsets/*immunology MH - Th1 Cells/immunology MH - Th2 Cells/immunology MH - Toll-Like Receptor 4/deficiency/*immunology MH - beta 2-Glycoprotein I/*immunology OTO - NOTNLM OT - APS OT - Anti-beta2-glycoprotein I antibody OT - Autoimmunity OT - Th cell OT - Toll-like receptor 4 EDAT- 2018/03/31 06:00 MHDA- 2019/05/06 06:00 CRDT- 2018/03/31 06:00 PHST- 2017/08/16 00:00 [received] PHST- 2018/02/12 00:00 [revised] PHST- 2018/03/23 00:00 [accepted] PHST- 2018/03/31 06:00 [pubmed] PHST- 2019/05/06 06:00 [medline] PHST- 2018/03/31 06:00 [entrez] AID - S0165-2478(17)30408-X [pii] AID - 10.1016/j.imlet.2018.03.010 [doi] PST - ppublish SO - Immunol Lett. 2018 Jun;198:17-25. doi: 10.1016/j.imlet.2018.03.010. Epub 2018 Mar 27.