REVIEW article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
This article is part of the Research TopicBiologics and Targeted Therapies for Autoimmune and Auto-inflammatory Dermatoses: Balancing Efficacy with Safety and ToxicityView all 17 articles
The SIRP Family: From Structural Diversity and Signaling Mechanisms to Implications in Immune-related Disease Targeted Therapeutics
Provisionally accepted
- Guangxi Normal University, Guilin, China
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Signal regulatory proteins (SIRPs) are membrane receptors on immune cells that control immune homeostasis and inflammation. Although SIRP family members share homologous extracellular domains, they differ in intracellular motifs and function: SIRPα transduces inhibitory signals, SIRPβ associates with DAP12 to trigger activation, and SIRPγ primarily modulates adhesion and T cell responses. This review compares the structure, ligand interactions, and signaling mechanisms of SIRPα, SIRPβ, and SIRPγ, summarizes their roles in cancer, autoimmunity and neurodegeneration, and surveys therapeutic strategies that target the CD47–SIRPα axis. We highlight current clinical progress, common toxicities, and open questions that must be addressed to advance SIRP-targeted therapies.
Keywords: autoimmune disease, cd47, Immune Regulation, Phagocytosis, SIRP family, tumor immune escape
Received: 09 Dec 2025; Accepted: 10 Feb 2026.
Copyright: © 2026 Jin, Huang, Song, Abideen, Tan, Xu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ming Chen
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