title: Cord blood monocyte-derived inflammatory cytokines suppress IL-2 and induce nonclassic "T(H)2-type" immunity associated with development of food allergy.
abstract: Food allergy is a major health burden in early childhood. Infants who develop food allergy display a proinflammatory immune profile in cord blood, but how this is related to interleukin-4 (IL-4)/T helper 2 (T(H)2)-type immunity characteristic of allergy is unknown. In a general population-derived birth cohort, we found that in infants who developed food allergy, cord blood displayed a higher monocyte to CD4(+) T cell ratio and a lower proportion of natural regulatory T cell (nT(reg)) in relation to duration of labor. CD14(+) monocytes of food-allergic infants secreted higher amounts of inflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor-α) in response to lipopolysaccharide. In the presence of the mucosal cytokine transforming growth factor-β, these inflammatory cytokines suppressed IL-2 expression by CD4(+) T cells. In the absence of IL-2, inflammatory cytokines decreased the number of activated nT(reg) and diverted the differentiation of both nT(reg) and naïve CD4(+) T cells toward an IL-4-expressing nonclassical TH2 phenotype. These findings provide a mechanistic explanation for susceptibility to food allergy in infants and suggest anti-inflammatory approaches to its prevention.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. The University of Melbourne, Parkville, Victoria 3010, Australia. Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China. yzhang@wehi.edu.au harrison@wehi.edu.au peter.vuillermin@deakin.edu.au.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Barwon Health, Geelong, Victoria 3220, Australia. Deakin University, Geelong, Victoria 3216, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: Collier
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Naselli
authors.affiliation: The University of Melbourne, Parkville, Victoria 3010, Australia. Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Saffery
authors.affiliation: The University of Melbourne, Parkville, Victoria 3010, Australia. Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia.
authors.forename: Mimi L K
authors.initials: ML
authors.lastname: Tang
authors.affiliation: The University of Melbourne, Parkville, Victoria 3010, Australia. Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia.
authors.forename: Katrina J
authors.initials: KJ
authors.lastname: Allen
authors.affiliation: The University of Melbourne, Parkville, Victoria 3010, Australia. Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia.
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Ponsonby
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. The University of Melbourne, Parkville, Victoria 3010, Australia. yzhang@wehi.edu.au harrison@wehi.edu.au peter.vuillermin@deakin.edu.au.
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Harrison
authors.affiliation: The University of Melbourne, Parkville, Victoria 3010, Australia. Barwon Health, Geelong, Victoria 3220, Australia. Deakin University, Geelong, Victoria 3216, Australia. Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia. yzhang@wehi.edu.au harrison@wehi.edu.au peter.vuillermin@deakin.edu.au.
authors.forename: Peter
authors.initials: P
authors.lastname: Vuillermin
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D005312:Fetal Blood / Q000166:cytology*; D005512:Food Hypersensitivity / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007223:Infant; D018836:Inflammation Mediators / Q000494:pharmacology*; D007376:Interleukin-2 / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D007376:Interleukin-2; D016212:Transforming Growth Factor beta