title: SOCS2 regulates T helper type 2 differentiation and the generation of type 2 allergic responses.
abstract: The incidence of allergy and asthma in developed countries is on the increase and this trend looks likely to continue. CD4(+) T helper 2 (Th2) cells are major drivers of these diseases and their commitment is controlled by cytokines such as interleukin 4, which are in turn regulated by the suppressor of cytokine signaling (SOCS) proteins. We report that SOCS2(-/-) CD4(+) T cells show markedly enhanced Th2 differentiation. SOCS2(-/-) mice, as well as RAG-1(-/-) mice transferred with SOCS2(-/-) CD4(+) T cells, exhibit elevated type 2 responses after helminth antigen challenge. Moreover, in in vivo models of atopic dermatitis and allergen-induced airway inflammation, SOCS2(-/-) mice show significantly elevated IgE, eosinophilia, type 2 responses, and inflammatory pathology relative to wild-type mice. Finally, after T cell activation, markedly enhanced STAT6 and STAT5 phosphorylation is observed in SOCS2(-/-) T cells, whereas STAT3 phosphorylation is blunted. Thus, we provide the first evidence that SOCS2 plays an important role in regulating Th2 cell expansion and development of the type 2 allergic responses.
authors.affiliation: The Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast BT9 7BL, Northern Ireland.
authors.forename: Camille A
authors.initials: CA
authors.lastname: Knosp
authors.forename: Helen P
authors.initials: HP
authors.lastname: Carroll
authors.forename: Joanne
authors.initials: J
authors.lastname: Elliott
authors.forename: Sean P
authors.initials: SP
authors.lastname: Saunders
authors.forename: Hendrik J
authors.initials: HJ
authors.lastname: Nel
authors.forename: Sylvie
authors.initials: S
authors.lastname: Amu
authors.forename: Joanne C
authors.initials: JC
authors.lastname: Pratt
authors.forename: Shaun
authors.initials: S
authors.lastname: Spence
authors.forename: Emma
authors.initials: E
authors.lastname: Doran
authors.forename: Nicola
authors.initials: N
authors.lastname: Cooke
authors.forename: Ruaidhri
authors.initials: R
authors.lastname: Jackson
authors.forename: Jonathan
authors.initials: J
authors.lastname: Swift
authors.forename: Denise C
authors.initials: DC
authors.lastname: Fitzgerald
authors.forename: Liam G
authors.initials: LG
authors.lastname: Heaney
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
authors.forename: Adrien
authors.initials: A
authors.lastname: Kissenpfennig
authors.forename: James A
authors.initials: JA
authors.lastname: Johnston
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage; D001249:Asthma / Q000209:etiology / Q000276:immunology; D001483:Base Sequence; D002454:Cell Differentiation / Q000276:immunology; D003876:Dermatitis, Atopic / Q000209:etiology / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D006967:Hypersensitivity / Q000145:classification / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000947:Antigens, Helminth; D007378:Interleukins; D012333:RNA, Messenger; D050791:STAT Transcription Factors; C491409:Socs2 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins