title: IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses.
abstract: Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina propria CD11b+ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24(+)CD64(-) DCs and contaminating CSF-1R-dependent CD24(-)CD64(+) macrophages. Functionally, loss of CD24(+)CD11b(+) DCs abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state and after Aspergillus fumigatus challenge. Human CD1c+ DCs, the equivalent of murine CD24(+)CD11b(+) DCs, also expressed IRF4, secreted IL-23, and promoted T helper 17 cell responses. Our data revealed heterogeneity in the mouse CD11b+ DC compartment and identifed mucosal tissues IRF4-expressing DCs specialized in instructing IL-17 responses in both mouse and human. The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in vivo findings to advance DC-based clinical therapies.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 138648 Singapore.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schlitzer
authors.forename: Naomi
authors.initials: N
authors.lastname: McGovern
authors.forename: Pearline
authors.initials: P
authors.lastname: Teo
authors.forename: Teresa
authors.initials: T
authors.lastname: Zelante
authors.forename: Koji
authors.initials: K
authors.lastname: Atarashi
authors.forename: Donovan
authors.initials: D
authors.lastname: Low
authors.forename: Adrian W S
authors.initials: AW
authors.lastname: Ho
authors.forename: Peter
authors.initials: P
authors.lastname: See
authors.forename: Amanda
authors.initials: A
authors.lastname: Shin
authors.forename: Pavandip Singh
authors.initials: PS
authors.lastname: Wasan
authors.forename: Guillaume
authors.initials: G
authors.lastname: Hoeffel
authors.forename: Benoit
authors.initials: B
authors.lastname: Malleret
authors.forename: Alexander
authors.initials: A
authors.lastname: Heiseke
authors.forename: Samantha
authors.initials: S
authors.lastname: Chew
authors.forename: Laura
authors.initials: L
authors.lastname: Jardine
authors.forename: Harriet A
authors.initials: HA
authors.lastname: Purvis
authors.forename: Catharien M U
authors.initials: CM
authors.lastname: Hilkens
authors.forename: John
authors.initials: J
authors.lastname: Tam
authors.forename: Michael
authors.initials: M
authors.lastname: Poidinger
authors.forename: E Richard
authors.initials: ER
authors.lastname: Stanley
authors.forename: Anne B
authors.initials: AB
authors.lastname: Krug
authors.forename: Laurent
authors.initials: L
authors.lastname: Renia
authors.forename: Baalasubramanian
authors.initials: B
authors.lastname: Sivasankar
authors.forename: Lai Guan
authors.initials: LG
authors.lastname: Ng
authors.forename: Matthew
authors.initials: M
authors.lastname: Collin
authors.forename: Paola
authors.initials: P
authors.lastname: Ricciardi-Castagnoli
authors.forename: Kenya
authors.initials: K
authors.lastname: Honda
authors.forename: Muzlifah
authors.initials: M
authors.lastname: Haniffa
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology*; D039481:CD11b Antigen / Q000378:metabolism; D051927:CD24 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D020381:Interleukin-17 / Q000096:biosynthesis / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D017452:Receptors, IgG / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000378:metabolism*; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
chemical_list: D039481:CD11b Antigen; D051927:CD24 Antigen; D050835:Interferon Regulatory Factors; D020381:Interleukin-17; D053759:Interleukin-23; D017452:Receptors, IgG; D051941:fms-Like Tyrosine Kinase 3; D000099218:Interferon Regulatory Factor-4; C497971:Flt3 protein, mouse