title: LZTFL1 Upregulated by All-Trans Retinoic Acid during CD4+ T Cell Activation Enhances IL-5 Production.
abstract: Retinoic acids, which are metabolites of vitamin A, have been shown to be involved in multiple T cell effector responses through their binding to the retinoic acid receptor, a ligand-activated transcription factor. Because the molecular mechanism of regulation by retinoic acid is still not fully uncovered, we investigated the gene expression profile of all-trans retinoic acid (ATRA)-treated human CD4(+) T cells. Leucine zipper transcription factor-like 1 (LZTFL1) was upregulated by ATRA in a dose- and time-dependent manner. The expression of LZTFL1 depended on both ATRA and TCR signaling. LZTFL1 accumulated in the plasma membrane compartment of human CD4(+) T cells, and, during immunological synapse formation, it transiently redistributed to the T cell and APC contact zone, indicating its role in T cell activation. Live-cell imaging demonstrates that at the initial stage of immunological synapse formation, LZTFL1 is concentrated at the APC contact site, and, during later stages, it relocates to the distal pole. Knockdown of LZTFL1 reduced the basal- and ATRA-induced levels of IL-5 in CD4(+) T cells, and overexpression of LZTFL1 enhanced the TCR-mediated NFAT signaling, suggesting that LZTFL1 is an important regulator of ATRA-induced T cell response. Together, these data indicate that LZTFL1 modulates T cell activation and IL-5 levels.
authors.affiliation: Laboratory of Molecular Cell Biology, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702; and.
authors.forename: Hong
authors.identifier: http://orcid.org/0000-0002-4502-233X
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Laboratory of Molecular Cell Biology, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702; and.
authors.forename: Kanyarat
authors.initials: K
authors.lastname: Promchan
authors.affiliation: Laboratory of Molecular Cell Biology, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702; and.
authors.forename: Bor-Ruei
authors.initials: BR
authors.lastname: Lin
authors.affiliation: Optical Microscopy and Analysis Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lockett
authors.affiliation: Optical Microscopy and Analysis Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702.
authors.forename: De
authors.initials: D
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Cell Biology, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702; and.
authors.forename: Heather
authors.initials: H
authors.lastname: Marshall
authors.affiliation: Laboratory of Molecular Cell Biology, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702; and.
authors.forename: Yunden
authors.initials: Y
authors.lastname: Badralmaa
authors.affiliation: Laboratory of Molecular Cell Biology, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702; and vnatarajan@mail.nih.gov.
authors.forename: Ven
authors.initials: V
authors.lastname: Natarajan
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D054992:Immunological Synapses / Q000187:drug effects / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D018613:Microscopy, Confocal; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000276:immunology*; D015533:Transcriptional Activation / Q000187:drug effects; D059467:Transcriptome; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: C508599:IL5 protein, human; D015848:Interleukin-5; C431701:LZTFL1 protein, human; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014212:Tretinoin