2. Academic Validation
  3. CGRP regulates macrophage polarization through JAK-STAT pathway to improve Hashimoto's thyroiditis

CGRP regulates macrophage polarization through JAK-STAT pathway to improve Hashimoto's thyroiditis

  • Int Immunopharmacol. 2026 May 1:176:116469. doi: 10.1016/j.intimp.2026.116469.
Yi Qin 1,  Tianyi Ni 2,  Wei Yan 3,  Yingying Wang 3,  Min Yi 4,  Liying Tu 4,  Yong Wang 5,  Qian Zhang 6
Affiliations

Affiliations

  • 1 Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210000, Jiangsu, PR China; Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 2 Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Urology, The Second Clinical Medical College of Nanjing Medical University, Nanjing, China.
  • 3 Department of Burn and Plastic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210000, Jiangsu, PR China.
  • 4 Department of Plastic Surgery, The Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu, PR China.
  • 5 Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210000, Jiangsu, PR China. Electronic address: [email protected].
  • 6 Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210000, Jiangsu, PR China. Electronic address: [email protected].
PMID: 41802370 DOI: 10.1016/j.intimp.2026.116469
Abstract

Background: Hashimoto's thyroiditis represents the most prevalent autoimmune thyroid disorder. It progresses from lymphocytic infiltration and elevated autoantibodies to late-stage hypothyroidism. Current therapies only manage hypothyroid symptoms without modifying disease progression. Calcitonin gene-related peptide demonstrates significant anti-inflammatory potential across immune disorders.

Objective: To investigate whether CGRP attenuates Hashimoto's thyroiditis by driving macrophage M2 polarization through JAK-STAT pathway activation.

Methods: We established murine Hashimoto's thyroiditis models comparing wild-type and CGRP-deficient mice. Histopathological analysis quantified inflammation severity. Serum autoantibodies were measured using ELISA. Inflammatory gene expression was assessed via qPCR. In vitro studies employed flow cytometry for macrophage phenotyping, Western blotting for JAK-STAT signaling, and cytokine ELISA. JAK Inhibitor interventions determined pathway dependence.

Results: Clinical data revealed reduced serum CGRP levels in Hashimoto's patients versus controls. CGRP deficiency exacerbated thyroid inflammation, elevated autoantibodies, and upregulated pro-inflammatory mediators in models. Mechanistically, CGRP promoted macrophage M2 polarization and suppressed inflammation through JAK-STAT activation. JAK inhibition abolished these effects.

Conclusion: CGRP alleviates autoimmune inflammation in Hashimoto's thyroiditis by activating JAK-STAT signaling to polarize macrophages toward M2 phenotypes. Therapeutic targeting of this axis may delay disease progression.

Keywords

Autoimmunity; CGRP; Hashimoto's thyroiditis; JAK-STAT; Thyroiditis.

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