IL-17 Family Signaling Pathway

Unknown IL-17B IL-17RB IL-17RA IL-17C IL-17RE IL-17A IL-17A/IL-17F IL-17F IL-17RA IL-17RC IL-17RA IL-17E IL-17RB IL-17RA Unknown IL-17RD

Background

The interleukin-17 (IL-17) family plays a critical role in the pathogenesis of autoimmune diseases, particularly in mediating tissue inflammation and autoimmune responses. This family comprises six members (IL-17A through IL-17F). IL-17A and IL-17F, as homodimers or heterodimers, bind the IL-17RA/IL-17RC receptor complex to activate NF-κB and MAPK signaling pathways, inducing the expression of multiple pro-inflammatory cytokines, chemokines, and antimicrobial peptides.

Among them, IL-17A has the most clearly defined role in autoimmune pathology. It is primarily produced by Th17 cells, γδ T cells, and innate lymphoid cells, and drives disease by promoting neutrophil recruitment and activation, as well as stimulating keratinocytes, fibroblasts, and synovial cells to produce inflammatory mediators. IL-17A is a key driver in the development of psoriasis, psoriatic arthritis, and ankylosing spondylitis. Clinical studies have demonstrated that anti-IL-17A monoclonal antibodies, such as secukinumab and ixekizumab, as well as anti-IL-17 receptor antibodies, such as brodalumab, significantly improve clinical symptoms and pathological changes in these diseases.

IL-17F exhibits similar but less potent pro-inflammatory activity and contributes to the maintenance of autoimmune inflammation. In contrast, IL-17E (IL-25) has distinct immune functions, primarily promoting Th2-type responses and playing a role in allergic and certain autoimmune conditions. The functions of other family members—IL-17B, IL-17C, and IL-17D—are less well defined, though early studies suggest involvement in mucosal immunity and the regulation of inflammatory responses.

Targeting the IL-17 signaling pathway has become an important therapeutic strategy for psoriasis, psoriatic arthritis, and ankylosing spondylitis, though its application in other autoimmune diseases remains under investigation. Further elucidation of IL-17 family functions will aid in the development of more precise treatment strategies for autoimmune disorders.