Identification of a novel type 2 innate immunocyte with the ability to enhance IgE production.

Fas (CD95), a member of the tumor necrosis factor receptor superfamily, mediates apoptosis-inducing signals in its expressing cells, especially in self-reactive cells. We recently reported that Fas(-/-) mice with a BALB/c background (BALB/c Fas(-/-) mice) developed blepharitis with allergic inflammation that was accompanied by hyper-IgE production. Here, we found a novel type of immunocyte in the spleen of BALB/c Fas(-/-) mice, which enhanced the production of IgE by B cells in the presence of IL-4 and CD40 signaling in vitro. The immunocyte did not express lineage markers but expressed Thy-1 and Sca-1 just like recently identified type 2 innate lymphoid cells, such as natural helper (NH) cells and nuocytes. However, they did not express c-Kit, IL-7R and IL-33R (T1/ST2), important markers of type 2 innate lymphoid cells. Instead, our identified Lin(-)Thy-1(+)Sca-1(+) cells expressed IL-18R and secreted Th2 cytokines when co-cultured with B cells or when stimulated with IL-18 and IL-2. Moreover, we found essentially the same type of cells in BALB/c wild-type mice as in BALB/c Fas(-/-) mice, which enhanced IgE production in contact with B cells in vitro. These cells from BALB/c wild-type mice expressed Fas and were sensitive to Fas-mediated apoptosis. Collectively, the newly identified Lin(-)Thy-1(+)Sca-1(+) cell, which we designated a F-NH cell (Fas-expressing natural helper cell), is a novel type 2 innate immunocyte with activity to enhance IgE production from B cells with the help of IL-4 and CD40 signaling. F-NH cells may play an important role in the development of chronic allergic inflammation.