title: All-trans-retinoic acid imprints expression of the gut-homing marker α4β7 while suppressing lymph node homing of dendritic cells.
abstract: Tissue-directed trafficking of dendritic cells (DCs) as natural adjuvants and/or direct vaccine carriers is highly attractive for the next generation of vaccines and immunotherapeutics. Since these types of studies would undoubtedly be first conducted using nonhuman primate models, we evaluated the ability of all-trans-retinoic acid (ATRA) to induce gut-homing α4β7 expression on rhesus macaque plasmacytoid and myeloid DCs (pDCs and mDCs, respectively). Induction of α4β7 occurred in both a time-dependent and a dose-dependent manner with up to 8-fold increases for mDCs and 2-fold increases for pDCs compared to medium controls. ATRA treatment was also specific in inducing α4β7 expression, but not expression of another mucosal trafficking receptor, CCR9. Unexpectedly, upregulation of α4β7 was associated with a concomitant downregulation of CD62L, a marker of lymph node homing, indicating an overall shift in the trafficking repertoire. These same phenomena occurred with ATRA treatment of human and chimpanzee DCs, suggesting a conserved mechanism among primates. Collectively, these data serve as a first evaluation for ex vivo modification of primate DC homing patterns that could later be used in reinfusion studies for the purposes of immunotherapeutics or mucosa-directed vaccines.
authors: Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, USA.
authors: Tristan I
authors: TI
authors: Evans
authors: R Keith
authors: RK
authors: Reeves
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D016023:Integrins / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D008253:Macaca mulatta; D002679:Pan troglodytes; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D016023:Integrins; C071777:integrin alpha4beta7; D014212:Tretinoin
references: J Exp Med. 2003 Sep 15;198(6):963-9
references: 12963696
references: Clin Vaccine Immunol. 2008 Jan;15(1):35-41
references: 17989338
references: Nat Immunol. 2004 Dec;5(12):1219-26
references: 15549123
references: Immunology. 1982 Jan;45(1):1-5
references: 6799390
references: Virology. 2007 Sep 1;365(2):356-68
references: 17490699
references: J Virol. 2011 Aug;85(16):8316-27
references: 21653670
references: J Med Primatol. 2010 Aug;39(4):235-42
references: 20618589
references: J Immunol. 2010 Nov 15;185(10):5915-25
references: 20944006
references: Eur J Immunol. 2011 Apr;41(4):1070-4
references: 21360701
references: Antioxid Redox Signal. 2011 Jan 15;14(2):261-73
references: 20524846
references: Cell. 2001 Aug 10;106(3):255-8
references: 11509172
references: Clin Exp Immunol. 1989 Mar;75(3):481-6
references: 2522844
references: J Immunol. 2007 Jun 1;178(11):6958-67
references: 17513745
references: Nat Immunol. 2008 Jul;9(7):769-76
references: 18516037
references: Immunity. 2004 Oct;21(4):527-38
references: 15485630
references: J Infect Dis. 2012 Nov;206(9):1462-8
references: 22711907
references: Nature. 2011 Mar 10;471(7337):220-4
references: 21307853
references: PLoS Pathog. 2009 May;5(5):e1000413
references: 19424421
references: J Virol. 2010 Sep;84(17):8959-63
references: 20554780
references: Clin Exp Immunol. 2002 Dec;130(3):404-8
references: 12452829
references: Nature. 2003 Jul 3;424(6944):88-93
references: 12840763
references: Clin Exp Immunol. 2013 Oct;174(1):109-19
references: 23607934