Article
The role of the interleukin (IL)-7/IL-7 receptor pathway in adult rheumatoid and juvenile idiopathic arthritis
Search Medline for
Authors
-
Tobias Schwarz
- University Hospital Würzburg, Department of Pediatrics, Pediatric Rheumatology and Special Immunology, Würzburg
-
Giovanni Almanzar
- University Hospital Würzburg, Department of Pediatrics, Pediatric Rheumatology and Special Immunology, Würzburg
-
Angelika Mutterer
- University Hospital Würzburg, Department of Pediatrics, Pediatric Rheumatology and Special Immunology, Würzburg
-
Sebastian Völkl
- University Hospital Würzburg, Department of Pediatrics, Pediatric Rheumatology and Special Immunology, Würzburg
-
Boris Hügle
- German Center for Pediatric and Adolescent Rheumatology, Garmisch-Partenkirchen
-
Johannes-Peter Haas
- German Center for Pediatric and Adolescent Rheumatology, Garmisch-Partenkirchen
-
Thomas Meyer
- University Hospital Würzburg, Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, Division of Pediatric Surgery, Würzburg
-
Christoph Pensko
- University Hospital Würzburg, Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, Division of Pediatric Surgery, Würzburg
-
Martin Feuchtenberger
- MVZ MED|BAYERN OST, Burghausen
-
Marc Schmalzing
- University Hospital Würzburg, Department of Internal Medicine II, Rheumatology/Clinical Immunology, Würzburg
-
Martina Prelog
- University Hospital Würzburg, Department of Pediatrics, Pediatric Rheumatology and Special Immunology, Würzburg
| Published: | September 18, 2024 |
|---|
Outline
Text
Methods: In this cross-sectional study, peripheral lymphocytes and serum samples were obtained from 36 patients with rheumatoid factor negative JIA, 24 juvenile healthy controls (jHC), 40 adults with seropositive RA, and 20 adult HC (aHC). Serum IL-7 concentrations were determined by ELISA. The proportions of CD127+ and activated CD25+ T-cells, as well as their proliferation, were assessed by flow-cytometry in untreated lymphocytes and following in vitro stimulation with recombinant human IL-7 (rhIL-7) for 6 days.
Results: IL-7 concentrations were significantly elevated in RA (median 47.0 pg/ml), compared to aHC (3.8 pg/ml, p<0.01), whereas IL-7 was not elevated in JIA (7.3 pg/ml, jHC 8.9 pg/ml). The proportion of CD4+ T-cells expressing CD127, however, was significantly reduced in RA (median 53.2%) compared to aHC (73.8%, p<0.001). This reduced expression of CD127 was dependent on disease activity (Inactive disease 58.4%, active disease 50.1%, p<0.01). In contrast to RA, JIA presented with an increased proportion of CD127+CD4+ T-cells (67.0%, jHC 53.1%, p<0.001), without any dependence on disease activity. Following stimulation with rhIL-7, CD127 was almost completely down-regulated in all cohorts. Whereas the rhIL-7 induced T-cell proliferation correlated with the native expression of CD127, the up-regulation of CD25 upon rhIL-7 was significantly lower within both rheumatic disease groups, compared to their respective HCs.
Conclusion: In RA, an increased disease-associated apoptotic loss of T-cells, which is described in the literature, presumably induces the elevated secretion of IL-7, which in turn causes the disease activity-associated downregulation of CD127. Future investigations may elucidate the interplay of IL-7 and T-cell-receptor stimulation in RA and JIA, resulting in the proliferation of autoreactive T-cells, and may identify IL-7 as a possible target for immunomodulatory therapy.
