Functional STAT3 deficiency compromises the generation of human T follicular helper cells
dc.contributor.author | Ma, Cindy | |
dc.contributor.author | Avery, Danielle T | |
dc.contributor.author | Chan, Anna | |
dc.contributor.author | Batten, Marcel L | |
dc.contributor.author | Bustamante, Jacinta | |
dc.contributor.author | Boisson-Dupuis, Stephanie | |
dc.contributor.author | Arkwright, Peter D | |
dc.contributor.author | Kreins, Alexandra Y | |
dc.contributor.author | Averbuch, Diana | |
dc.contributor.author | Engelhard, Dan | |
dc.contributor.author | Cook, Matthew | |
dc.contributor.author | Deenick, Elissa | |
dc.contributor.author | Tangye, Stuart | |
dc.date.accessioned | 2015-12-10T23:02:11Z | |
dc.date.issued | 2012 | |
dc.date.updated | 2016-06-14T08:36:38Z | |
dc.description.abstract | T follicular helper (Tfh) cells are critical for providing the necessary signals to induce differentiation of B cells into memory and Ab-secreting cells. Accordingly, it is important to identify the molecular requirements for Tfh cell development and function. We previously found that IL-12 mediates the differentiation of human CD4 + T cells to the Tfh lineage, because IL-12 induces naive human CD4 + T cells to acquire expression of IL-21, BCL6, ICOS, and CXCR5, which typify Tfh cells. We have now examined CD4 + T cells from patients deficient in IL-12Rp1, TYK2, STAT1, and STAT3 to further explore the pathways involved in human Tfh cell differentiation. Although STAT1 was dispensable, mutations in IL12RB1, TYK2, or STAT3 compromised IL-12-induced expression of IL-21 by human CD4 + T cells. Defective expression of IL-21 by STAT3-deficient CD4 + T cells resulted in diminished B-cell helper activity in vitro. Importantly, mutations in STAT3, but not IL12RB1 or TYK2, also reduced Tfh cell generation in vivo, evidenced by decreased circulating CD4 +CXCR5 + T cells. These results highlight the nonredundant role of STAT3 in human Tfh cell differentiation and suggest that defective Tfh cell development and/or function contributes to the humoral defects observed in STAT3-deficient patients. | |
dc.identifier.issn | 0006-4971 | |
dc.identifier.uri | http://hdl.handle.net/1885/61901 | |
dc.publisher | American Society of Hematology | |
dc.source | Blood | |
dc.subject | Keywords: chemokine receptor CXCR5; interleukin 12; interleukin 12 receptor beta1; interleukin 21; protein bcl 6; protein kinase TYK2; STAT1 protein; STAT3 protein; adolescent; adult; article; B lymphocyte; CD4+ T lymphocyte; cell line; cell lineage; cell maturatio | |
dc.title | Functional STAT3 deficiency compromises the generation of human T follicular helper cells | |
dc.type | Journal article | |
local.bibliographicCitation.issue | 17 | |
local.bibliographicCitation.lastpage | 4008 | |
local.bibliographicCitation.startpage | 3997 | |
local.contributor.affiliation | Ma, Cindy, Garvan Institute of Medical Research | |
local.contributor.affiliation | Avery, Danielle T, Garvan Institute of Medical Research | |
local.contributor.affiliation | Chan, Anna , Garvan Institute of Medical Research | |
local.contributor.affiliation | Batten, Marcel L, Garvan Institute of Medical Research | |
local.contributor.affiliation | Bustamante, Jacinta, Necker Medical School, University of Paris Descartes | |
local.contributor.affiliation | Boisson-Dupuis, Stephanie, Necker Medical School, University of Paris Descartes | |
local.contributor.affiliation | Arkwright, Peter D, University of Manchester | |
local.contributor.affiliation | Kreins, Alexandra Y, The Rockefeller University | |
local.contributor.affiliation | Averbuch, Diana, Hadassah-Hebrew University Medical Centre | |
local.contributor.affiliation | Engelhard, Dan, Hadassah-Hebrew University Medical Centre | |
local.contributor.affiliation | Cook, Matthew, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Ma, Cindy , Garvan Institute of Medical Research | |
local.contributor.affiliation | Deenick, Elissa, Garvan Institute of Medical Research | |
local.contributor.affiliation | Tangye, Stuart, Garvan Institute of Medical Research | |
local.contributor.authoremail | u2572788@anu.edu.au | |
local.contributor.authoruid | Cook, Matthew, u2572788 | |
local.description.embargo | 2037-12-31 | |
local.description.notes | Imported from ARIES | |
local.identifier.absfor | 110200 - CARDIOVASCULAR MEDICINE AND HAEMATOLOGY | |
local.identifier.ariespublication | f5625xPUB649 | |
local.identifier.citationvolume | 119 | |
local.identifier.doi | 10.1182/blood-2011-11-392985 | |
local.identifier.scopusID | 2-s2.0-84859711557 | |
local.identifier.thomsonID | 000305282900021 | |
local.identifier.uidSubmittedBy | f5625 | |
local.type.status | Published Version |
Downloads
Original bundle
1 - 1 of 1
No Thumbnail Available
- Name:
- 01_Ma_Functional_STAT3_deficiency_2012.pdf
- Size:
- 583.94 KB
- Format:
- Adobe Portable Document Format