| Presentation preference | Oral presentation |
| Title | Sex-specific unconventional neutrophils determine immunological outcome in Behçet's uveitis |
| Purpose | Behçet's disease (BD) is a multi-systemic inflammatory vasculitis, with a high incidence and more serious course of intraocular inflammation (Behçet's uveitis, BU) in males. However, the etiology of male-biased Behçet's uveitis is largely unknown. |
| Methods | The retrospective study on 1,881 BU patients was performed to assess the sex-differences in the clinical manifestations and their correlation with neutrophils. Single cell sequencing was used to identify the sex-specific heterogeneity in neutrophil composition under normal and BU conditions at single-cell resolution. Neutrophil-specific genetic knockouts and transfer experiments were performed to determine the function of aberrant neutrophil subsets in vivo. |
| Results | The retrospective study on BU revealed male-biased exacerbated neutrophil responses and worse long-term prognosis. Male BU was enriched for conventional inflammatory neutrophil subsets compared with female BD, whereas unconventional neutrophil subsets characterized by IFN-α signaling and regulation of T cell activation were decreased. Mechanistically, we found that IFN-α2a treatment expanded circulating unconventional neutrophils and in turn induced the expansion of regulatory T cells. These results substantiate the therapeutic effect of IFN-α2a on the Behçet's uveitis pathogenesis. Accordingly, we further confirmed unconventional neutrophil subsets were able to directly regulate Th17 and Treg cell balance in EAU. |
| Conclusion | Our single-cell atlas defined sex-specific and disease-specific neutrophil heterogeneity in Behçet's uveitis pathogenesis and provided a resource characterizing the role of neutrophils in regulating peripheral immune homeostasis and Behçet's uveitis pathogenesis. |
| Conflict of interest | No |
Authors 1
| Last name | WANG |
| Initials of first name(s) | QF |
| Department | The First Affiliated Hospital of Chongqing Medical University |
| City | Chongqing |
| Country | China |
Authors 2
| Last name | Gao |
| Initials of first name(s) | Y |
| Department | Shanxi Medical University |
| City | Taiyuan |
| Country | China |
Authors 3
| Last name | Yang |
| Initials of first name(s) | PZ |
| Department | The First Affiliated Hospital of Chongqing Medical University |
| City | Chongqing |
| Country | China |
