Figure 8.

Possible cellular and molecular mechanisms of Mycobacteria-mediated colitis. The differential production of CXCR3 ligands and their recognition by CXCR3⁺ cells are involved in Mycobacteria-enhanced colitis. Regulatory T cells (Tr1) are critical to maintain tolerance or homeostasis in the presence of commensal flora. In a host (e.g., IL-10^-/- or NOD2/CARD15 or TLR polymorphisms) that is deficient in the regulation of tolerance, inactive dendritic cells (iDC) mature and aid in the differentiation of precursor T helper cells (pT) to Th1 cells. These Th1 cells express CXCR3, TNF-α, and IFN-γ, while mature dendritic cells (mDC) and other activated antigen-presenting cells express CXCR3, CXCL9, CXCL11, and IL-12p40 to support Th1 development as well as the recruit of CXCR3- and CXCL10-expressing cells (e.g., CD8⁺ T cells, polymorphonuclear cells (PMN), natural killer (NK) and NK T cells (NKT)) for the propagation and recurrence of IBD, which correlates with increases in SAA, CXCR3 ligands, and anti-Mycobacteria IgG1 and IgG2 Abs.