Th2skewed

Th2-skewed describes an immune profile in which CD4+ T cells preferentially differentiate toward the T helper 2 (Th2) lineage, resulting in a cytokine milieu dominated by IL-4, IL-5, and IL-13. This bias promotes B cell class switching to IgE, eosinophil recruitment, mucus production, and humoral immunity, while dampening Th1-type responses and intracellular pathogen defense. Th2 differentiation is driven by IL-4 and transcription factor GATA3, with cross-regulation by cytokines from other lineages.

In clinical terms, Th2-skewing is commonly associated with allergic diseases such as atopic dermatitis, allergic rhinitis, and asthma, and with helminth infections. It may influence responses to vaccines and infections, favoring antibody-mediated over cell-mediated immunity. In tumors and chronic infections, a Th2-dominant environment can be linked to reduced cytotoxic T cell activity, though the role is context-dependent.

Assessment of Th2 skewing uses serum IgE levels, eosinophilia, and local or systemic cytokine profiles showing IL-4, IL-5, IL-13, as well as transcriptional markers like GATA3. Genetic and environmental factors can bias toward Th2, including certain polymorphisms in IL4, IL4R, STAT6, and exposure patterns early in life, infections, or microbiome composition.

Therapeutically, interventions that modulate Th2 responses, such as anti-IL-4/IL-13 agents or anti-IL-5 therapies, are used in allergic diseases. However, Th2 responses are part of a broader immune network; plasticity among T helper subsets means skewing can shift with context and may have unintended consequences.