Interleukin-10 Is Produced by a Specific Subset of Taste Receptor Cells and Critical for Maintaining Structural Integrity of Mouse Taste Buds

Abstract

Although inflammatory responses are a critical component in defense against pathogens, too much inflammation is harmful. Mechanisms have evolved to regulate inflammation, including modulation by the anti-inflammatory cytokine interleukin-10 (IL-10). Previously we have shown that taste buds express various molecules involved in innate immune responses, including the proinflammatory cytokine tumor necrosis factor (TNF). Here, using a reporter mouse strain, we show that taste cells also express the anti-inflammatory cytokine IL-10. Remarkably, IL-10 is produced by only a specific subset of taste cells, which are different from the TNF-producing cells in mouse circumvallate and foliate taste buds: IL-10 expression was found exclusively in the G-protein gustducin-expressing bitter receptor cells, while TNF was found in sweet and umami receptor cells as reported previously. In contrast, IL-10R1, the ligand-binding subunit of the IL-10 receptor, is predominantly expressed by TNF-producing cells, suggesting a novel cellular hierarchy for regulating TNF production and effects in taste buds. In response to inflammatory challenges, taste cells can increase IL-10 expression both in vivo and in vitro. These findings suggest that taste buds use separate populations of taste receptor cells that coincide with sweet/umami and bitter taste reception to modulate local inflammatory responses, a phenomenon that has not been previously reported. Furthermore, IL-10 deficiency in mice leads to significant reductions in the number and size of taste buds, as well as in the number of taste receptor cells per taste bud, suggesting that IL-10 plays critical roles in maintaining structural integrity of the peripheral gustatory system.

Regulation of bitter taste responses by tumor necrosis factor

“…Our studies have found that several inflammation-associated cytokines are preferentially expressed in taste bud cells compared to nontaste lingual epithelial cells (Cohn et al, 2010; Feng et al, 2014a; Feng et al, 2014b; Feng et al, 2012; Kim et al, 2012; Wang et al, 2007), suggesting that these cytokines may have special functions in the peripheral taste system. In particular, we have found that TNF is specifically expressed in a subset of taste bud cells even in healthy mice (Feng et al, 2012; Kim et al, 2012).…”

“…Interferon-γ is expressed in a subset of type II and III taste cells (Kim et al, 2012). The anti-inflammatory cytokine IL-10 is expressed in type II bitter cells (Feng et al, 2014a). Whether these cytokines are involved in taste sensing remains largely unknown.…”

Taste bud-derived BDNF maintains innervation of a subset of TrkB-expressing gustatory nerve fibers

“…For instance, glial cell line-derived neurotrophic factor is expressed in a different subset of taste bud cells than BDNF (Suzuki et al, 2007; Takeda et al, 2004), and its receptors are expressed in the geniculate ganglion (Farbman et al, 2004b; Yamout et al, 2005). However, many other factors could also play this role/s (Feng et al, 2014; Germana et al, 2006; McLaughlin, 2000; Suzuki et al, 2007; Suzuki et al, 2005; Takeda et al, 2005; Yee et al, 2005). …”

The effect of imiquimod on taste bud calcium transients and transmitter secretion

“…Notably, inflammation appears to play a role in many of the conditions and diseases associated with taste impairments (Zhu et al , ; Kumarhia et al , ). These studies suggest that immune responses may play a role for maintaining structural integrity of taste buds (Kim et al , ; Feng et al , ); however, little information has been generated regarding inflammation–taste interactions.…”