IL4 homeostasis is regulated by innate T cells

Abstract

Helper T cell balance is important in shaping a proper immune repertoire against intracellular or extracellular antigens. B6 and BALB/c mice are representative Th1 and Th2-dominant strains, and they are very distinct in their immunological nature. Compared to B6 mice, BALB/c mice have more than a 100-fold higher serum IgE levels but are less efficient in developing Th1 responses. As a Th2 response requires IL4 for its initiation, we tracked the cells providing IL4 at the steady state and identified iNKT cells as a source of IL4 in BALB/c mice. 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.