Figure 4.

An Amphiregulin‐mediated autocrine activation of the epidermal growth factor receptor (EGFR) facilitates T‐cells to form a hetero‐complex with the IL‐33R (T1/ST2), which enables IL‐33 to activate the mitogen‐activated protein kinase (MAPK) signalling pathway. The low‐affinity EGFR ligand Amphiregulin activates resting EGFR complexes. This places the receptor into a ‘poised state’, which allows it to enter ‘signalling competent’ clusters on the cell surface and to interact with the IL‐33R (T1/ST2). Such clusters of hetero‐complexes between the EGFR and T1/ST2 then enables IL‐33 to mediate a MAPK‐mediated signal via the EGFR, and thus potentially the proliferation of tissue‐resident regulatory T‐cell populations. AREG, Amphiregulin.