The study involved BREATH researchers Christine Ehlers and Dr. Dr. Theresa Graalmann, both from the Center for Experimental and Clinical Infection Research Twincore in Hannover and from the Department of Rheumatology and Immunology at Hannover Medical School (MHH), as well as Prof. Dr. Jonas Schupp and PD Dr. Benjamin Seeliger from the Department of Pneumology and Infectious Diseases at MHH.

The team examined blood samples and bronchoalveolar lavage (BAL) fluid from individuals with systemic sclerosis (SSc) or Sjögren’s syndrome (SjD), as well as from healthy controls, using high-resolution spectral flow cytometry. The goal of the study was to identify immunological and metabolic alterations that contribute to the development and persistence of interstitial lung disease (ILD) in the context of these systemic conditions.

The analyses revealed marked differences in immune cell profiles between the two diseases: In the peripheral blood of patients with SSc, the proportion of terminally differentiated CD4⁺ effector memory T cells (TEMRA) was significantly increased. These cells displayed reduced mitochondrial activity—an indication of dysregulated energy metabolism associated with a chronically activated but functionally exhausted immune status. In contrast, Sjögren’s syndrome was characterized by a reduction in cytotoxic CD8⁺ T cells and increased expression of the activation marker CD25 on memory T cells, likewise suggesting sustained immune stimulation.

Particularly informative were the investigations of the BAL samples, which allow direct insights into immunological processes within the lung. In individuals with SSc- or SjD-associated ILD, there was an accumulation of CD8⁺ T cells exhibiting a CD69⁺/PD-1⁺ phenotype—a pattern typically observed in chronically activated and exhausted T cells. These cells may play a crucial role in maintaining inflammation within lung tissue. Additionally, the researchers detected heightened activation of type 2 conventional dendritic cells (cDC2), characterized by increased expression of HLA-DR and co-stimulatory molecules. These cDC2 cells may serve as key antigen-presenting cells driving local T-cell activation and sustaining the immune response.

The findings clearly demonstrate that autoimmune-associated lung manifestations are not driven solely by local tissue damage but by complex systemic immune processes. The combination of disturbed T-cell metabolism, exhaustion markers, and altered differentiation points to chronic antigen exposure contributing to disease progression. “The data show how tightly interconnected immunometabolism and the functional plasticity of T cells are—and that this axis has been underestimated in autoimmune-associated lung manifestations,” explains Dr. Theresa Graalmann, senior author of the publication.

The study highlights the strength of interdisciplinary research between rheumatology and pneumology in Hannover. It provides valuable new insights into the mechanisms of immune-mediated lung disease and establishes a foundation for future strategies aimed at developing targeted biomarkers and immunomodulatory therapies.

Original publication:

Ehlers C, Biermann H, Thiele T, et al. T cells of patients with systemic sclerosis or Sjögren's disease display an aberrant metabolic state and memory phenotype in blood and lungs. Rheumatology (Oxford). 2025;64(8):4806-4815. doi:10.1093/rheumatology/keaf198

Text: BREATH/ AB

Foto: TWINCORE/ T. Damm