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Cell and Gene Therapy 2018 & Clinical Microbiology Congress 2018
Biomedical Research
|
ISSN: 0976-1683
|
Volume 29
S e p t e m b e r 1 0 - 1 1 , 2 0 1 8 | D u b l i n , I r e l a n d
allied
academies
Joint Event on
CLINICAL AND MEDICAL MICROBIOLOGY
CELL AND GENE THERAPY
&
World Congress on
International Conference on
Biomed Res 2018, Volume 29 | DOI: 10.4066/biomedicalresearch-C3-008
FC
γ
RIIIA IS A DISTINCT ACTIVATING COSIGNAL IN CD4+ T CELLS THAT
SYNERGIZE WITH TLR9
Anil K Chauhan
University of Iowa, USA
W
e have been exploring the mechanistic insight of the stimulatory effects of Fc
γ
RIIIa cosignaling in human CD4
+
T-cells. CD4
+
T
cells also express FcγRIIa and these cells accumulateHIV provirus. We have previously shown that Fc
γ
RIIIa cosignal participate
in relocating endosomal NA-TLRs to the cell surface, where they can recognize modified self-nucleic acid. Joint signaling from
Fc
γ
RIIIa and TLR9 (CpG ODN 2006) enhances IL-17A, IL-21 production. Now, we show that Fc
γ
RIIIa cosignaling generate a new
subset that show Syk phosphorylation and express TFH markers i.e. Bcl6, CXCR5, ICOS and PD1. In HIV infection, blood TFH cells
do not express Bcl6+, contrary to this finding we observed Bcl6 in blood pSyk+ T cells
in vivo
in systemic lupus erythematosus
(SLE) and in
in vitro
. Bcl6+ cells in blood produce IFN-
γ
, IL-17A and IL-21. The Syk inhibitor block IL-21 production. pSyk+ cells show
moderate PD1 expression compared to a second population that express high PD1. Our RNA-seq data show differential expression
of lincRNA and microRNA from Fc
γ
RIIIa cosignaling that contribute to T cell differentiation. A key finding was upregulation of
mir
1307, a recognized risk allele for SLE in GWAS studies. We propose that Fc
γ
RIIIa drives epigenetic changes in CD4+ T cells.
Transcription factors c-Maf, FOXO were upregulated. Fc
γ
RIIIa cosignal modulated ubiquitination, HSPs, proteasome assembly, and
GPCR signaling. Our data provide new insight into the FcR biology in adaptive responses and raises several interesting questions.
Does FcRs bearing effector CD4+ T cells superior helper, for the development of autoreactive B cells?