title: B cell-intrinsic and -extrinsic regulation of antibody responses by PARP14, an intracellular (ADP-ribosyl)transferase.
abstract: The capacity to achieve sufficient concentrations of Ag-specific Ab of the appropriate isotypes is a critical component of immunity that requires efficient differentiation and interactions of Ag-specific B and Th cells along with dendritic cells. Numerous bacterial toxins catalyze mono(ADP-ribosyl)ation of mammalian proteins to influence cell physiology and adaptive immunity. However, little is known about biological functions of intracellular mammalian mono(ADP-ribosyl)transferases, such as any ability to regulate Ab responses. poly-(ADP-ribose) polymerase 14 (PARP14), an intracellular protein highly expressed in lymphoid cells, binds to STAT6 and encodes a catalytic domain with mammalian mono(ADP-ribosyl)transferase activity. In this article, we show that recall IgA as well as the STAT6-dependent IgE Ab responses are impaired in PARP14-deficient mice. Whereas PARP14 regulation of IgE involved a B cell-intrinsic process, the predominant impact on IgA was B cell extrinsic. Of note, PARP14 deficiency reduced the levels of Th17 cells and CD103⁺ DCs, which are implicated in IgA regulation. PARP14 enhanced the expression of RORα, Runx1, and Smad3 after T cell activation, and, importantly, its catalytic activity of PARP14 promoted Th17 differentiation. Collectively, the findings show that PARP14 influences the class distribution, affinity repertoire, and recall capacity of Ab responses in mice, as well as provide direct evidence of the requirement for protein mono-ADP-ribosylation in Th cell differentiation.
authors: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors: Sung Hoon
authors: SH
authors: Cho
authors: Ariel
authors: A
authors: Raybuck
authors: Mei
authors: M
authors: Wei
authors: John
authors: J
authors: Erickson
authors: Ki Taek
authors: KT
authors: Nam
authors: Reagan G
authors: RG
authors: Cox
authors: Alyssa
authors: A
authors: Trochtenberg
authors: James W
authors: JW
authors: Thomas
authors: John
authors: J
authors: Williams
authors: Mark
authors: M
authors: Boothby
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011065:Poly(ADP-ribose) Polymerases / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology
chemical_list: D007070:Immunoglobulin A; C522628:Parp14 protein, mouse; D011065:Poly(ADP-ribose) Polymerases
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