title: AIRE expressing marginal zone dendritic cells balances adaptive immunity and T-follicular helper cell recruitment.
abstract: Autoimmune polyendocrine syndrome Type I (APS I) results in multiple endocrine organ destruction and is caused by mutations in the Autoimmune regulator gene (AIRE). In the thymic stroma, cells expressing the AIRE gene dictate T cell education and central tolerance. Although this function is the most studied, AIRE is also expressed in the periphery in DCs and stromal cells. Still, how AIRE regulated transcription modifies cell behaviour in the periphery is largely unknown. Here we show that AIRE is specifically expressed by 33D1(+) DCs and dictates the fate of antibody secreting cell movement within the spleen. We also found that AIRE expressing 33D1(+) DCs expresses self-antigens as exemplified by the hallmark gene insulin. Also, as evidence for a regulatory function, absence of Aire in 33D1(+) DCs led to reduced levels of the chemokine CXCL12 and increased co-stimulatory properties. This resulted in altered activation and recruitment of T-follicular helper cells and germinal centre B cells. The altered balance leads to a change of the early response to a T cell-dependent antigen in Aire(-/-) mice. These findings add to the understanding of how specific DC subtypes regulate the early responses during T cell-dependent antibody responses within the spleen and further define the role of AIRE in the periphery as regulator of self-antigen expression and lymphocyte migration.
authors.affiliation: Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
authors.forename: Evelina
authors.initials: E
authors.lastname: Lindmark
authors.forename: Yunying
authors.initials: Y
authors.lastname: Chen
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Georgoudaki
authors.forename: Diana
authors.initials: D
authors.lastname: Dudziak
authors.forename: Emma
authors.initials: E
authors.lastname: Lindh
authors.forename: William C
authors.initials: WC
authors.lastname: Adams
authors.forename: Karin
authors.initials: K
authors.lastname: Loré
authors.forename: Ola
authors.initials: O
authors.lastname: Winqvist
authors.forename: Benedict J
authors.initials: BJ
authors.lastname: Chambers
authors.forename: Mikael C I
authors.initials: MC
authors.lastname: Karlsson
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D020566:Dendritic Cells, Follicular / Q000276:immunology*; D007108:Immune Tolerance / Q000235:genetics; D007328:Insulin / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000096927:AIRE Protein
chemical_list: D054377:Chemokine CXCL12; D007328:Insulin; D014157:Transcription Factors; D000096927:AIRE Protein