Browsing by Author "Kreins, Alexandra Y."
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Item Functional STAT3 deficiency compromises the generation of human T follicular helper cells(The American Society of Hematology, 2012-04-26) 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; 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.; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Pediatri Anabilim Dalı.; 0000-0001-8571-2581; AAH-1658-2021; 34975059200T 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-12R beta 1, 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.Item A patient with tyrosine kinase 2 deficiency without hyper-IgE syndrome(Mosby-Elsevier, 2012-06) Boisson, Stephanie Dupuis; Kreins, Alexandra Y.; Grant, Audrey V.; Abel, Laurent; Casanova, Jean-Laurent; Kılıç, Sara Şebnem; Hacımustafaoğlu, Mustafa; Uludağ Üniversitesi/Tıp Fakültesi/Pediatri Anabilim Dalı.; 0000-0001-8571-2581; AAH-1658-2021; 34975059200; 6602154166We describe a Turkish patient with tyrosine kinase 2 deficiency who suffered from disseminated Bacille Calmette-Guerin infection, neurobrucellosis, and cutaneous herpes zoster infection. Tyrosine kinase 2 deficiency should be considered in patients susceptible to herpes viruses and intramacrophage pathogens even in the absence of atopy, high serum IgE, and staphylococcal disease.