Person: Ramesh, Narayanaswamy
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Publication A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP
(The Rockefeller University Press, 2012) Lanzi, Gaetana; Moratto, Daniele; Vairo, Donatella; Masneri, Stefania; Delmonte, Ottavia; Paganini, Tiziana; Parolini, Silvia; Tabellini, Giovanna; Mazza, Cinzia; Savoldi, Gianfranco; Montin, Davide; Martino, Silvana; Tovo, Pierangelo; Pessach, Itai M.; Massaad, Michel; Ramesh, Narayanaswamy; Porta, Fulvio; Plebani, Alessandro; Notarangelo, Luigi; Geha, Raif; Giliani, SilviaA homozygous mutation that gave rise to a stop codon in the WIPF1 gene resulted in WASP protein destabilization and in symptoms resembling those of Wiskott-Aldrich syndrome
Publication DOCK8 Functions as an Adaptor that Links TLR–MyD88 Signaling to B Cell Activation
(Nature Publishing Group, 2012) Rauter, Ingrid; Recher, Mike; Wakim, Rima; Dbaibo, Ghassan; Dasouki, Majed; Barlan, Isil; Baris, Safa; Kutukculer, Necil; Ochs, Hans; Plebani, Alessandro; Kanariou, Maria; Lefranc, Gerard; Reisli, Ismail; Fitzgerald, Katerine; Golenbock, Douglas; Keles, Sevgi; Ceja, Reuben; Jabara, Haifa Halim; McDonald, Douglas; Janssen, Erin; Massaad, Michel; Ramesh, Narayanaswamy; Borzutzky, Arturo; Benson, Halli Louise; Schneider, Lynda; Baxi, Sachin; Notarangelo, Luigi; Al-Herz, Waleed; Manis, John; Chatila, Talal; Geha, RaifDOCK8 and MyD88 have been implicated in serologic memory. Here we report antibody responses were impaired and (CD27^+) memory B cells were severely reduced in DOCK8-deficient patients. Toll-like receptor 9 (TLR9)- but not CD40-driven B cell proliferation and immunoglobulin production were severely reduced in DOCK8-deficient B cells. In contrast, TLR9-driven expression of AICDA, CD23 and CD86, and activation of NF-κB, p38 and Rac1 were intact. DOCK8 associated constitutively with MyD88 and the tyrosine kinase Pyk2 in normal B cells. Following TLR9 ligation, DOCK8 became tyrosine phosphorylated by Pyk2, bound the Src family kinase Lyn and linked TLR9 to a Src-Syk-STAT3 cascade essential for TLR9-driven B cell proliferation and differentiation. Thus, DOCK8 functions as an adaptor in a TLR9-MyD88 signaling pathway in B cells.