Functional STAT3 deficiency compromises the generation of human T follicular helper cells

Ma, Cindy S., Avery, Danielle T., Chan, Anna, Batten, Marcel, Bustamante, Jacinta, Boisson-Dupuis, Stephanie, Arkwright, Peter D., Kreins, Alexandra Y., Averbuch, Diana, Engelhard, Dan, Magdorf, Klaus, Kilic, Sara S., Minegishi, Yoshiyuki, Nonoyama, Shigeaki, French, Martyn A., Choo, Sharon, Smart, Joanne M., Peake, Jane, Wong, Melanie, Gray, Paul, Cook, Matthew C., Fulcher, David A., Casanova, Jean-Laurent, Deenick, Elissa K. and Tangye, Stuart G. (2012) Functional STAT3 deficiency compromises the generation of human T follicular helper cells. Blood, 119 17: 3997-4008.

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Author Ma, Cindy S.
Avery, Danielle T.
Chan, Anna
Batten, Marcel
Bustamante, Jacinta
Boisson-Dupuis, Stephanie
Arkwright, Peter D.
Kreins, Alexandra Y.
Averbuch, Diana
Engelhard, Dan
Magdorf, Klaus
Kilic, Sara S.
Minegishi, Yoshiyuki
Nonoyama, Shigeaki
French, Martyn A.
Choo, Sharon
Smart, Joanne M.
Peake, Jane
Wong, Melanie
Gray, Paul
Cook, Matthew C.
Fulcher, David A.
Casanova, Jean-Laurent
Deenick, Elissa K.
Tangye, Stuart G.
Total Author Count Override 25
Title Functional STAT3 deficiency compromises the generation of human T follicular helper cells
Formatted title Functional STAT3 deficiency compromises the generation of human T follicular helper cells
Journal name Blood  (ERA 2012 Listed)    (ERA 2010 Rank A*)   Check publisher's open access policy
Publication date 2012-04-26
Sub-type Article
DOI 10.1182/blood-2011-11-392985
Volume number 119
Issue number 17
ISSN 0006-4971
1528-0020
Start page 3997
End page 4008
Total pages 12
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Collection year 2013
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 8 March 2012.

Document type: Journal Article
Sub-type: Article
Collections: Official 2013 Collection
School of Medicine Publications
 
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Created: Wed, 14 Mar 2012, 10:37:25 EST by Melanie Thomas on behalf of Paediatrics & Child Health - RBWH