title: CD103(+) Dendritic Cells Control Th17 Cell Function in the Lung.
abstract: Th17 cells express diverse functional programs while retaining their Th17 identity, in some cases exhibiting a stem-cell-like phenotype. Whereas the importance of Th17 cell regulation in autoimmune and infectious diseases is firmly established, the signaling pathways controlling their plasticity are undefined. Using a mouse model of invasive pulmonary aspergillosis, we found that lung CD103(+) dendritic cells (DCs) would produce IL-2, dependent on NFAT signaling, leading to an optimally protective Th17 response. The absence of IL-2 in DCs caused unrestrained production of IL-23 and fatal hyperinflammation, which was characterized by strong Th17 polarization and the emergence of a Th17 stem-cell-like population. Although several cell types may be affected by deficient IL-2 production in DCs, our findings identify the balance between IL-2 and IL-23 productions by lung DCs as an important regulator of the local inflammatory response to infection.
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore; Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy. Electronic address: teresa.zelante@unipg.it.
authors.forename: Teresa
authors.initials: T
authors.lastname: Zelante
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore; National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456, Singapore.
authors.forename: Alicia Yoke Wei
authors.initials: AY
authors.lastname: Wong
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
authors.forename: Tang Jing
authors.initials: TJ
authors.lastname: Ping
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
authors.forename: Jinmiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
authors.forename: Hermi R
authors.initials: HR
authors.lastname: Sumatoh
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
authors.forename: Elena
authors.initials: E
authors.lastname: Viganò
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hong Bing
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
authors.forename: Bernett
authors.initials: B
authors.lastname: Lee
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zolezzi
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore; Integrated Center for Cell Therapy and Regenerative Medicine (ICCT), International Clinical Research Center, St. Anne's University Hospital Brno, Brno 65691, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Fric
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
authors.forename: Evan W
authors.initials: EW
authors.lastname: Newell
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mortellaro
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Puccetti
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore. Electronic address: paola.castagnoli@gmail.com.
authors.forename: Paola
authors.initials: P
authors.lastname: Ricciardi-Castagnoli
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001228:Aspergillosis / Q000276:immunology* / Q000473:pathology; D001230:Aspergillus / Q000276:immunology; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D039001:Integrin alpha Chains / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D007376:Interleukin-2; D050778:NFATC Transcription Factors; C091367:alpha E integrins; D019703:Calcineurin; D002118:Calcium