Role of Leptin and Ghrelin in Induction of Differentiation of IL-17-Producing and T-Regulatory Cells

Abstract

We studied isolated and combined effects of leptin and ghrelin on the formation of IL-producing and T-regulatory cells. Leptin in concentrations comparable with its normal blood concentration during pregnancy (trimester II-III) promotes differentiation of peripheral blood CD4(+) cells to IL-17-producing cells and enhances IL-17A production, but suppresses the formation of T-regulatory cells in vitro. In contrast, ghrelin in a concentration typical of trimester I-II of pregnancy reduces the number of IL-17-producing cells, but stimulated the formation of T-regulatory cells. The effects of leptin and ghrelin in combination typical of trimester I-II of pregnancy stimulated the formation of T-regulatory cells, while in combination typical of trimester II-III did not shift the balance of T-regulatory cells and IL-17-producing cells, but stimulated the formation of IL-17A. We conclude that leptin and ghrelin play an important role in the maintenance of the balance of IL-17-producing and T-regulatory cells during pregnancy.

Leptin/osteopontin axis contributes to enhanced T helper 17 type responses in allergic rhinitis

“…18 Several recent studies also reported the positive role of leptin or leptin receptor in Th17 differentiation. [24][25][26] However, Moraes's study found that leptin decreases CD4+ Foxp3+ and CD4 + IL-17+ cell frequency in the draining lymph nodes of immunized mice but increases subsequent delayed-type hypersensitivity responses. 27 This discrepancy may arise from different experimental condition and definition of CD4+ T cells in different studies.…”

Erythromycin inhibits neutrophilic inflammation and mucosal disease by upregulating DEL-1

“…In line with the finding that GHSR was required for the ability of ERM to upregulate DEL-1, ghrelin also enhanced DEL-1 expression and exerted a similar antiinflammatory effect as ERM in the lungs after intratracheal challenge with a sublethal dose of LPS. Similar to DEL-1, which is a potent antagonist of IL-17 induction (13,17,18,20,21), ghrelin was earlier shown to inhibit IL-17 responses (41,42). Future studies are warranted for a better understanding of the potential relationship between DEL-1 and ghrelin in regulating IL-17 responses and how they might antagonize leptin, which promotes Th17 differentiation and IL-17 production (42,43).…”

Obesity, Fat Mass and Immune System: Role for Leptin

“…In collagen-induced arthritis mouse model, articular injection of leptin (5 μg) increased the number of Th17 in the joint tissue, resulting in exacerbating joint inflammation, and consequently early onset of arthritis and increased disease severity ( Deng et al, 2012 ). Leptin, in concentrations similar to that found in blood during pregnancy, promoted the differentiation of peripheral blood CD4+ cells to Th17 cells, but suppressed the formation of Treg cells in vitro ( Orlova and Shirshev, 2014 ). CD4+ T cell-derived leptin, but not plasma leptin, were positively correlated with the percentage of Th17 cells or RORγt levels in chronic lymphocytic thyroiditis, an organ-specific autoimmune disease ( Wang et al, 2013 ).…”