Details

Autor(en) / Beteiligte

• Sharma, Sribava
• Tomar, Sunil
• Dharne, Mayuri
• Ganesan, Varsha
• Smith, Andrew
• Yang, Yanfen
• Waggoner, Lisa
• Wang, Yui-Hsi
• Hogan, Simon P

Titel

Deletion of [DELTA]dblGata motif leads to increased predisposition and severity of IgE-mediated food-induced anaphylaxis response

Ist Teil von

• PloS one, 2019-08, Vol.14 (8), p.e0219375

Ort / Verlag

Public Library of Science

Erscheinungsjahr

2019

Quelle

Elektronische Zeitschriftenbibliothek - Freely accessible e-journals

Beschreibungen/Notizen

• Previous studies have revealed an important role for the transcription factor GATA-1 in mast cell maturation and degranulation. However, there have been conflicting reports with respect to the requirement of GATA-1 function in mast cell dependent inflammatory processes. Herein, we examine the requirement of GATA-1 signaling in mast cell effector function and IgE-mast cell-dependent anaphylaxis. To study the requirement of GATA-1 dependent signaling in the development and severity of IgE-mast cell-dependent anaphylaxis in mice. Wild type (Balb/c) and mutant [DELTA]dblGata (Balb/c) mice were employed to study the role of GATA-1 signaling in in vitro IgE-mediated activation of bone marrow derived mast cells (BMMCs). Murine models of passive IgE-mediated and oral antigen-induced IgE-mediated anaphylaxis were employed in mice. Frequency of steady state mast cells in various tissues (duodenum, ear, and tongue), peritoneal cavity, and clinical symptoms (diarrhea, shock, and mast cell activation) and intestinal Type 2 immune cell analysis including CD4.sup.+ Th.sub.2 cells, type 2 innate lymphoid cells (ILC2), and IL-9 secreting mucosal mast cells (MMC9) were assessed In vitro analysis revealed that [DELTA]dblGata BMMCs exhibit a reduced maturation rate, decreased expression of Fc[epsilon]RI[alpha], and degranulation capacity when compared to their wildtype (WT) counterparts. These in vitro differences did not impact tissue resident mast cell numbers, total IgE, and susceptibility to or severity of IgE-mediated passive anaphylaxis. Surprisingly, [DELTA]dblGata mice were more susceptible to IgE-mast cell-mediated oral antigen induced anaphylaxis. The increased allergic response was associated with increased Type 2 immunity (antigen-specific IgE, and CD4.sup.+ T.sub.H 2 cells), MMC9 cells and small intestine (SI) mast cell load. Diminished GATA-1 activity results in reduced in vitro mast cell Fc[epsilon]RI[alpha] expression, proliferation, and degranulation activity. However, in vivo, diminished GATA-1 activity results in normal homeostatic tissue mast cell levels and increased antigen-induced CD4.sup.+ Th2 and iMMC9 cell levels and heightened IgE-mast cell mediated reactions.