The emerging role of the hedgehog signaling pathway in immunity response and autoimmune diseases

The Hedgehog (Hh) family is a prototypical morphogen involved in embryonic patterning, multi-lineage differentiation, self-renewal, morphogenesis, and regeneration. There are studies that have demonstrated that the Hh signaling pathway differentiates developing T cells into MHC-restricted self-antigen tolerant T cells in a concentration-dependent manner in the thymus. Whereas Hh signaling pathway is not required in the differentiation of B cells but is indispensable in maintaining the regeneration of hematopoietic stem cells (HSCs) and the viability of germinal centers (GCs) B cells. The Hh signaling pathway exerts both positive and negative effects on immune responses, which involves activating human peripheral CD4⁺ T cells, regulating the accumulation of natural killer T (NKT) cells, recruiting and activating macrophages, increasing CD4⁺Foxp3⁺ regulatory T cells in the inflammation sites to sustain homeostasis. Hedgehog signaling is involved in the patterning of the embryo, as well as homeostasis of adult tissues. Therefore, this review aims to highlight evidence for Hh signaling in the differentiation, function of immune cells and autoimmune disease. Targeting Hh signaling promises to be a novel, alternative or adjunct approach to treating tumors and autoimmune diseases.