New immunologic pathways in the pathogenesis of leprosy: Role for Th22 cytokines in the polar forms of the disease

Advances in the Immunology and Genetics of Leprosy

“…IL-9 was found to be expressed more highly in TT lesions compared to LL lesions (81), consistent with the early finding that IL-9 could promote anti-M. leprae cytotoxicity (82). In contrast, the expression of Th22 signatures IL-22 and fibroblast growth factor basic (FGF-b) was higher in LL lesions compared to TT lesions (83).…”

Leprosy As a Complex Infection: Breakdown of the Th1 and Th2 Immune Paradigm in the Immunopathogenesis of the Disease

“…In situ , the Th22 lymphocyte response has gained fundamental importance in the lepromatous form of the disease, because FGF b can regulate different cellular functions that can interfere with the processes of cicatrization, migration, cell division, proliferation, differentiation, and angiogenesis. In these circumstances, the increase of FGF b in the lepromatous form of the disease reinforces the crucial role of this growth factor in development of the reparative response, since this clinical form is associated with greater bacillary spread, greater tissue damage, and, consequently, a greater number of injuries ( 11 , 81 ).…”

“…Among the cytokines that compose the response profile of the cell, IL-22 has been particularly highlighted in leprosy owing to the fact that in the lepromatous form, this cytokine participates in the mechanisms of maturation of the phagolysosome. Indeed, in macrophages infected by the bacillus, IL-22 was shown to modulate the production of calgranulin A, thereby increasing the intracellular concentrations of Ca 2+ as well as Rab7 ( 81 ). As a detriment to the development of a macrophage response, IL-22 induces the production of STAT3 as well as iNOS that destroy the bacillus ( 82 ).…”

Leprosy is teaching us the immunopathogenesis of inflammatory skin disease

“…1 T-cell plasticity changes among different subsets, and is increased in chronic stimulation states or with increased disease severity. 2 T H 17 to T H 1 as well as other T-cell subset plasticity has been demonstrated in the past. 3 T H 22 was originally described as a separated clone with a unique genome transcriptome that functionally differentiates it from T H 1, T H 2, and T H 17.…”

“…The T H 22 subset has been discovered in leprosy, with increased IL-22 in T H 2 anergic lepromatous leprosy and decreased IL-22 in T H 1 tuberculoid leprosy with intact cell-mediated immunity. 2 The increase in IL-22 at the T H 2 lepromatous pole corresponds to the increase in IL-22 in T H 2 atopic dermatitis versus T H 1 psoriasis. 1 T H 22 is well established in both T H 1 psoriasis and T H 2 atopic dermatitis.…”