AUTHOR=Gao Yingying , Peng Guoyuan , Liu Xin , Ren Xiaochen , Chen Xiaoxiang , Zhan Yifan 

TITLE=Enhancing the treatment potential of IL-17 antagonism in lupus nephritis: finding the right partner

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1617451

DOI=10.3389/fimmu.2025.1617451

ISSN=1664-3224

ABSTRACT=The treatment of lupus nephritis (LN) has been benefiting from biologics targeting immune cells and cytokines. IL-17 antagonists have been investigated for their potential in LN treatment, with mixed results from case reports and randomized controlled trials. Here we provide an overview of the contributions of various immune cells and kidney resident cells to LN pathogenesis and discuss relevant biologics for LN treatment. We then explore our current understanding of IL-17 and IL-17-producing cells in LN pathogenesis and examine the status of IL-17 antagonists in LN treatment. Given the limited success in clinical studies with IL-17 antagonism alone for LN, we discuss possible rational combination biologic therapies, with a focus on the potential combination with antagonism of IL-36, a cytokine family associated with SLE disease activity. Thus, emerging evidence suggests that dual biologic therapy could enhance disease control in LN.