Circulating T Cell Subsets and ILC2s are Altered in Patients With Chronic Rhinosinusitis With Nasal Polyps After Dupilumab Treatment.

BACKGROUND

Chronic rhinosinusitis with nasal polyps (CRSwNP) is mainly associated with type 2 inflammation and is often unmanageable, regardless of the treatment. Dupilumab, a monoclonal antibody targeting the interleukin (IL)-4 receptor alpha to inhibit IL-4 and IL-13 signaling, has recently been shown to significantly improve the condition of patients with CRSwNP. However, the mechanisms underlying this response to dupilumab are not yet fully understood.

OBJECTIVE

We sought to examine whether circulating T cell subset proportions and their functions are altered by dupilumab treatment.

METHODS

We first investigated the proportion of circulating T cell subsets and group 2 innate immune cells (ILC2s) in patients with CRSwNP treated with dupilumab using mass and flow cytometry. We then assessed cytokine gene expression and cytokine production in peripheral blood mononuclear cells (PBMCs) using quantitative reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA).

RESULTS

The type 2 T helper (Th2) cell proportion significantly decreased after dupilumab treatment, whereas that of type 1 T helper (Th1) cells increased. Moreover, programmed death-1 (PD-1) expression in regulatory T (Treg) cells was significantly reduced. The proportion of ILC2s significantly increased after dupilumab treatment. Unfortunately, neither cytokine gene expression nor cytokine production in PBMCs showed significant changes.

CONCLUSIONS

Our findings suggest that in CRSwNP patients treated with dupilumab, Th2, Treg, and ILC2 cells, which regulate type 2 inflammation, are modulated in the peripheral circulation. Further analysis of circulating immune cells could provide novel insights into understanding the pathophysiologic mechanisms of dupilumab and the development of tailored therapeutic strategies for patients with CRSwNP.