Person:
Janssen, Erin

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Janssen

First Name

Erin

Name

Janssen, Erin

Filters

2012 - 20182

Settings

Author's Publications: search.filters.isAuthorOfPublication.a363348f-9825-4d15-8cd0-d3642c9fad4c

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    WASP-mediated regulation of anti-inflammatory macrophages is IL-10 dependent and is critical for intestinal homeostasis
    (Nature Publishing Group UK, 2018) Biswas, Amlan; Shouval, Dror S.; Griffith, Alexandra; Goettel, Jeremy; Field, Michael; Kang, Yu Hui; Konnikova, Liza; Janssen, Erin; Redhu, Naresh; Thrasher, Adrian J.; Chatila, Talal; Kuchroo, Vijay; Geha, Raif; Notarangelo, Luigi D.; Pai, Sung-Yun; Horwitz, Bruce; Snapper, Scott
    Mutations in Wiskott–Aldrich syndrome protein (WASP) cause autoimmune sequelae including colitis. Yet, how WASP mediates mucosal homeostasis is not fully understood. Here we show that WASP-mediated regulation of anti-inflammatory macrophages is critical for mucosal homeostasis and immune tolerance. The generation and function of anti-inflammatory macrophages are defective in both human and mice in the absence of WASP. Expression of WASP specifically in macrophages, but not in dendritic cells, is critical for regulation of colitis development. Importantly, transfer of WT anti-inflammatory macrophages prevents the development of colitis. DOCK8-deficient macrophages phenocopy the altered macrophage properties associated with WASP deficiency. Mechanistically, we show that both WASP and DOCK8 regulates macrophage function by modulating IL-10-dependent STAT3 phosphorylation. Overall, our study indicates that anti-inflammatory macrophage function and mucosal immune tolerance require both WASP and DOCK8, and that IL-10 signalling modulates a WASP-DOCK8 complex.
  • Thumbnail Image
    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, Raif
    DOCK8 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.