A hierarchy of affinities between cytokine receptors and the common gamma chain leads to pathway cross-talk

作者：Gonnord Pauline; Angermann Bastian R; Sadtler Kaitlyn; Gombos Erin; Chappert Pascal; Meier Schellersheim Martin^*; Varma Rajat^*

来源：Science Signaling, 2018, 11(524): eaal1253.

DOI：10.1126/scisignal.aal1253

Cytokines belonging to the common gamma chain (gamma(c)) family depend on the shared gamma(c) receptor subunit for signaling. We report the existence of a fast, cytokine-induced pathway cross-talk acting at the receptor level, resulting from a limiting amount of gamma(c) on the surface of T cells. We found that this limited abundance of gamma(c) reduced interleukin-4 (IL-4) and IL-21 responses after IL-7 preexposure but not vice versa. Computational modeling combined with quantitative experimental assays indicated that the asymmetric cross-talk resulted from the ability of the "private" IL-7 receptor subunits (IL-7R alpha) to bind to many of the gamma(c) molecules even before stimulation with cytokine. Upon exposure o

• 出版日期2018-4-3
• 单位MIT; NIH