NKT cells regulate IgE production through homeostatic IL4 secretion

Abstract

Despite IgE is one of major indicators of atopic or allergic disorders, its steady state regulation is not well understood. Serum level of IgE is dependent on IL4 cytokine and, compared to B6 mice, BALB/c mice have more than a 100-fold higher serum IgE levels. We tracked the cells providing IL4 at the steady state in BALB/c mice and identified iNKT cells as a source of it. Through intracellular staining for transcription factors, we have defined three subsets of iNKT cells (NKT1, NKT2 and NKT17) that produced IFN, IL4 and IL17 respectively. NKT2 cells were particularly enriched in BALB/c mice and were localized thymic medulla and T cell zone of spleen and lymph node. Comprehensive genetic analysis revealed NKT subsets share more genetic signatures with those of  T and innate lymphoid cells (ILCs) rather than conventional helper T cells. Collectively these results suggest innate lineage T cell, including iNKT and  T cells do pivotal roles regulating IL4 homeostasis and IgE production.