Notable Publication: Increased CD8+ Tissue Resident Memory T cells, Regulatory T cells and Activated Natural Killer Cells in Systemic Sclerosis Lungs

The UPMC Division of Rheumatology and Clinical Immunology’s Cristina Padilla, MD, Robert Lafyatis, MD, Tracy Tabib, MS, Banafsheh Nazari, MS, and Patrizia Fuschiotti, PhD, recently published a study in Rheumatology (Oxford) that identifies and analyzes the lymphoid subpopulations in systemic sclerosis (SSc)-interstitial lung disease (ILD).

Other collaborators included faculty from the UPMC Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine and the Division of Pulmonary, Critical Care, and Sleep Medicine at the Ohio State University College of Medicine.

Study Abstract¹

Background

While there is evidence demonstrating that lymphocytes help drive autoimmunity in SSc, it is unclear how specific lymphocyte subtypes, T and NK cells, function in SSc-ILD lung tissue. Therefore, the goal of this research was to assess how lymphocytes appear in SSc-ILD lung explants.

Methods

Lymphoid populations from 13 SSc-ILD and six healthy control (HC) lung explants were analyzed using Seurat, a toolkit for quality control, analysis, and exploration of single cell RNA sequencing data. Lymphoid clusters were identified by their differential gene expression. Cell numbers and size in each cluster were compared between cohorts. Researchers conducted additional analysis using pathway analysis, pseudotime, and cell ligand-receptor interactions.

Results

Activated CD16+ NK cells, CD8+ tissue resident memory T cells, and Treg cells were proportionately higher in SSc-ILD compared with HC lungs. Activated CD16+ NK cells in SSc-ILD showed upregulated granzyme B, IFN-γ, and CD226. Amphiregulin, highly upregulated by NK cells, was predicted to interact with epidermal growth factor receptor on several bronchial epithelial cell populations. Shifts in CD8+ T cell populations indicated a transition from resting to effector to tissue resident phenotypes in SSc-ILD.

Conclusion

The study results showed that SSc-ILD lungs do have activated lymphoid populations. The presence of activated cytotoxic NK cells suggest that they may play a role in alveolar epithelial cell loss, while their upregulated expression of amphiregulin suggests they may also induce bronchial epithelial cell hyperplasia. CD8+ T cells in SSc-ILD appear to transition from resting to the tissue resident memory phenotype.

Reference and Full Study Access

1. Padilla CM, Valenzi E, Tabib T, Nazari B, Sembrat J, Rojas M, Fuschiotti P, Lafyatis R. Increased CD8+ tissue resident memory T cells, regulatory T cells and activated natural killer cells in systemic sclerosis lungs. Rheumatology (Oxford). 2024 Mar 1;63(3):837-845. doi: 10.1093/rheumatology/kead273. PMID: 37310903; PMCID: PMC10907815.