During lymphopenia, peripheral T cells undergo a process termed ‘homeostatic proliferation’ to maintain the immune system while giving rise to the possibility of an aberrant expansion of autoreactive clones.83,84 Under this circumstance, a two-hit model driven by commensal microbiota has been proposed to explain the pathogenesis of lymphopenia-associated colitis.85 First, the microbiota stimulates innate cell production of IL-6 via MyD88, which provides signals for the spontaneous proliferation of T cells. The gene discussed is IL6; the disease is lymphopenia.