# Single-immunocyte transcriptomics reveal the role of natural killer cell-dependent exogenous antigen presentation in ankylosing spondylitis severity

## TL;DR

The study reveals that natural killer cells contribute to ankylosing spondylitis severity through antigen presentation, offering new insights into immune mechanisms driving the disease.

## Contribution

The novel finding is the role of APC-NK cells in exogenous antigen presentation linked to AS severity and progression.

## Key findings

- APC-NK abundance and antigen presentation scores increase during AS aggravation but decrease during remission.
- HLA-DPB1/DPA1 in APC-NK mediates antigen presentation targeting CD4+ T cells, contributing to AS severity.
- NK cell exhaustion improves AS-like mouse phenotypes, suggesting a therapeutic potential.

## Abstract

Ankylosing spondylitis (AS) is an autoimmune disease that can cause severe deformities, and the immunological patterns associated with its onset and progression remain poorly understood. Here, after recruiting healthy donors and patients in different stages, we performed single-cell RNA sequencing for peripheral blood mononuclear cells to investigate the cytotaxonomic and immunological hallmarks associated with AS onset, aggravation and remission and explore the intrinsic laws causing AS lesions. The results showed that innate antibacterial defense functions were generally enhanced in most cell types at disease onset and were negatively associated with AS severity. The abundance and exogenous antigen presentation scores of the natural killer (NK) cell subset characterized as antigen-presenting cells (APC-NK) increased during disease aggravation but decreased during remission. Generally, APC-NK abundance and their presentation scores were negatively correlated with innate defense scores for multiple cell types. CD4+ effector T cell abundance and cytotoxicity, as well as the enhancement of CD4+ T cell responses by HLA-DRB1+ NK cells (similar to APC-NK), were associated with AS severity. The implantation of HLA-DRB1+ NK cells accelerated AS-like alterations in SKG modeling mice with curdlan induction; this was blocked with CD4+ T cell exhaustion. NK cell exhaustion improved the phenotypes of AS-like mice. HLA-DPB1/DPA1 in APC-NK participated in AS aggravation by mediating antigen presentation targeting CD4+ T cells. Overall, innate defense antigen presentation coupling drives AS lesions and different outcomes. Furthermore, the trade-off between innate defense and NK-dependent exogenous antigen presentation results in CD4+ T cell activation or inactivation, thereby contributing to AS aggravation or remission; this reveals that APC-NK is a crucial factor causing ankylosing deformities.

Ankylosing spondylitis (AS) is a chronic disease affecting the spine and joints, often leading to disability. Current treatments mainly focus on symptom relief, but understanding the disease’s underlying causes is crucial for better therapies. Researchers aimed to explore the immune processes involved in AS using advanced techniques such as single-cell RNA sequencing. The study involved 14 patients with AS and 3 healthy donors. Researchers collected blood samples and analyzed immune cells to understand their roles in AS. They found that certain immune cells, including T cells and natural killer cells, behave differently in patients with AS compared with healthy individuals. These differences are linked to the disease’s progression and severity. The study revealed that immune responses, particularly those involving NK cells, play a significant role in AS. These findings suggest that targeting specific immune pathways could improve treatment strategies.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.