Human T2R38 Bitter Taste Receptor Expression in Resting and Activated Lymphocytes

Abstract

The human G-protein-coupled bitter taste receptor T2R38 has recently been demonstrated to be expressed on peripheral blood neutrophils, monocytes and lymphocytes. To further define a potential contribution of the T2R38 receptor in adaptive immune response, the objective of this study was to analyze its expression in resting and activated lymphocytes and T cell subpopulations. Freshly isolated PBMC from healthy donors were used for expression analysis by flow cytometry. Quantum™ MESF beads were applied for quantification in absolute fluorescence units. Activation methods of T cells were anti-CD3/CD28, phytohaemagglutinin (PHA) or phorbol 12-myristate 13-acetate (PMA) together with ionomycin. Lymphocytes from young donors expressed higher levels of T2R38 compared to the elderly. CD3+ T cells expressed higher levels that CD19+ B cells. Receptor expression followed T cell activation with an upregulation within 24 h and a peak at 72 h. Higher levels of T2R38 were produced in lymphocytes by stimulation with anti-CD3/CD28 compared to PHA or PMA/ionomycin. Both subpopulations of CD4+ as well as CD8+ T cells were found to express the T2R38 receptor; this was higher in CD4+ than CD8+ cells; the amount of T2R38 in central and effector memory cells was higher as compared to naïve cells, although this was not statistically significant for CD8+ cells without prior activation by anti-CD3/CD28. Upon treatment of PBMC with the natural T2R38 agonist goitrin Calcium flux was activated in the lymphocyte population with functional T2R38 receptor at >20 μM which was completely blocked by phospholipase Cβ-2 inhibitor U73211. Further, goitrin selectively inhibited TNF-alpha secretion in PBMC with functional T2R38. This quantitative analysis of T2R38 expression in distinct PBMC subsets may provide a basis for understanding the significance of bitter compounds in immune modulation. Whether these findings can have implications for the treatment of inflammatory and immunologic disorders by bitter tasting pharmaceuticals or foods needs further investigation.

Existing bitter medicines for fighting 2019‐nCoV‐associated infectious diseases

“…Moreover, some required genes for bitter‐sensing, such as α‐gustducin and Trpm5, are also critical to initiate a type 2 immune response 30,31 . Human lymphocytes also directly express TAS2R 32 . These reports are consistent with our results.…”

Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells

“…Despite the mechanism and the specific TAS2R involved in each process remains to be elucidated, our data suggests that "bitter" molecules present endogenously in the BM microenvironment, such as amino acids (71,72), or extrinsic factors, such as drugs (42,73), might interact with TAS2Rs and affect leukemia cell functions. Since, previous data (74) and our unpublished observations indicated that TAS2R were expressed also in healthy hematopoietic cells, we could speculate that TAS2R may represent a novel receptor-based pathway by which blood cells "taste" their microenvironment and respond to it accordingly.…”

Taste receptor polymorphisms and longevity: a systematic review and meta-analysis

“…have been claimed to mediate an anti-inflammatory effect [22,23]. Because of the well-known role of both an efficient immune response and an optimal control of inflammation in the attainment of longevity [24,25], these mechanisms might explain the association of TAS2R with longevity.…”