TNF and colitis: While NHE3-/- mice develop distal colitis primarily via activation of innate immune mechanisms without a significant engagement of effector T cells [24], loss of B and T lymphocytes, and presumably the associated loss of regulatory T cells (Treg), led to higher mucosal expression TNFα, IFNγ, IL1β, and NOS2 in the distal colon of DKO mice, as compared with WT, Rag2-/-, or NHE3-/- strains (Fig 1).