[초청강연] Induction of Natural IgE by Glucocorticoids

Allergy is one of the most prevalent chronic diseases, affecting hundreds of millions of people
worldwide. In allergy, environmental allergens such as pollen or peanut induce B cells to undergo
class switch recombination and produce Immunoglobulin E (IgE) antibodies. IgE is a key molecule
that mediates allergic responses by coating mast cell surfaces and inducing mast cell
degranulation upon binding a specific allergen. IgE can also be spontaneously produced in the
absence of exogenous allergens, yet the biogenesis and functions of such “natural” IgE still
remains largely unknown. Here, we discovered that glucocorticoids, steroid stress hormones,
enhance IgE isotype class switching in B cells both in vivo and in vitro. This IgE class switching
is directly promoted by B cell-intrinsic glucocorticoid receptor signaling that synergizes with the
IL-4/STAT6 pathway. In addition, we found that rare B cells residing in the mesenteric lymph
nodes are responsible for the production of glucocorticoid-inducible IgE, which is associated with
the depletion of the gut microbiota. Notably, mice preemptively treated with glucocorticoids were
protected from subsequent IgE-mediated pathogenic anaphylaxis in vivo. We furthermore
demonstrated that natural IgE may have a high affinity for the Fc epsilon receptor I (FceRI) on
mast cells, and can therefore competitively interfere with the binding of pathogenic IgE during
anaphylaxis. Thus, our results suggest that glucocorticoids, classically considered to be
immunosuppressive, hold an immunostimulatory role in B cells instead, which could be a new
therapeutic target to alleviate allergic responses.