Background Type 2 innate lymphoid cells (ILC2) and M2 polarized macrophages are activated and produce cytokines in response to IL-25/IL-17RB, although the relevance of this axis to immune responses in primary Sjoren's syndrome (pSS) is unknown.

Objectives We sought to investigate the role of the IL-25/IL-17RB axis and ILC2 and M2 macrophages in patients with pSS.

Methods Expression analysis of IL-17B, IL-25, IL-33 and IL-17RB was performed by TaqMan real-time PCR and immunohistochemistry on salivary glands from 50 patients and 20 controls. Analysis of IL-17RB expression and the frequencies of natural type 2 innate lymphoid cells (nILC2), inflammatory ILC2 (iILC2), and M2-polarized macrophages were assessed by means of flow cytometry among salivary gland (SGMC) and peripheral blood (PBMC) mononuclear cells. Clusters of ILC2 cells and M2 macrophages were also studied by immunohistochemistry and confocal microscopy. The role of IL-25 on ILC2 was investigated in ex vivo studies.

Results IL-25 and IL-17RB, but not IL-25, were significantly over-expressed in the MSG of pSS patients and correlated with the focus score and the degree of lymphoid organization. IL-17RB was mainly expressed by T lymphocytes, ILC2 cells and macrophages. No significant increased expression of IL-33 was observed in pSS. Significant increase in the frequency of iILC2, but not of nILC2, was observed in both PBMC and SGMC. Clusters of ILC2 cells, resembling fat associated lymphoid clusters (FLAC), and M2 polarization were also observed in pSS salivary glands and correlated with the focus score. IL-25 stimulation of isolated SGMC and PBMC resulted in the expansion of iILC2.

Conclusions These findings suggest that IL-25 may promote, by interacting locally and sistemically with IL-17RB⁺ cells, an iILC2 and M2 inflammatory state in pSS. Blockade of the IL-25 axis could be clinically relevant in pSS.

Disclosure of Interest None declared