Targeted IL-4Rα blockade ameliorates refractory allergic eosinophilic inflammation in a patient with dysregulated TGF-β signaling due to ERBIN deficiency

Transforming growth factor-beta (TGF-β) is a multifunctional cytokine that possesses immune stimulatory and inhibitory functions, influences T-lymphocyte differentiation, and promotes cell proliferation and wound healing.1 This TGF-β signaling activates the transcription factor SMAD3, which increases interleukin-4 (IL-4) receptor expression associated with type 2–skewed immune responses (Figure 1). Dysregulated TGF-β signaling has been implicated in human syndromes with coexistent connective tissue abnormalities and atopy (eg, Ehlers-Danlos syndrome, Loeys-Dietz syndrome).