Question

1. True/False: Individuals with mutations in the genes encoding the IL-12p40 subunit (shared by IL-12 and IL-23) are susceptible to not only pathogens such as M. tuberculosis that require a Th1 response, but type 3 (Th17) responses are also affected.

Answer 1

True

RNA-activated APCs secrete IL-12 (a major cytokine) to generateTh1 response thereby causing pathogenesis of TB. Though the most active form is IL-12p70 (produced by DCs, macrophages, and neutrophils), knocking out IL-12p40 attributes to less DC migration to the draining lymph node thereby causing reduction in level of activated CD4+ T-cells 7 antigen-presentation and hence the reduced inability to control mycobacterial growth. Impaired IL-12- and IFNγ-dependent pathway of APC activation and CD4+ T-cell differentiation causes pro-inflammatory effect of an activation of Th1 cells.

The IL-12p40 (also subunit of IL-23 receptor) forms Th17 cells and thus both T cells can be grouped as Th1/Th17 compartment. Deficiency in IL-17 decreases levels of IFNγ, thereby defining the role of Th17 in initial mycobacterial infection and how it is impacted further by the IFNγ-dependent pathway of APC activation and CD4+ T-cell differentiation