impact factor, citescore
logo
 

Full Papers

 

JAK/STAT inhibition modifies the ILC1 immune response in patients with rheumatoid arthritis


1, 2, 3, 4, 5, 6, 7

 

  1. Biomedicine, Neuroscience and Advanced Diagnostic, University of Palermo, Italy.
  2. Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Rheumatology Section, P. Giaccone University of Palermo, Italy.
  3. Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Rheumatology Section, P. Giaccone University of Palermo, Italy.
  4. Biomedicine, Neuroscience and Advanced Diagnostic, University of Palermo, Italy.
  5. Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Rheumatology Section, P. Giaccone University of Palermo, Italy.
  6. Department of Precision Medicine, Rheumatology Section, University of Campania Luigi Vanvitelli, Naples, Italy.
  7. Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Rheumatology Section, P. Giaccone University of Palermo, Italy. giuliana.guggino@unipa.it

CER16504
Full Papers

purchase article

PMID: 37812490 [PubMed]

Received: 06/01/2023
Accepted : 02/08/2023
In Press: 21/09/2023

Abstract

OBJECTIVES:
Recent evidence suggests that innate lymphoid cells (ILCs) might be involved in rheumatoid arthritis (RA) pathogenesis and individuals at risk of RA exhibited an increased frequency of ILC1. JAK3 participates in ILC1 and ILC3 differentiation. Tofacitinib and the Janus Kinase (JAK) 3 inhibitor, PF-06651600, impair the ability of human intraepithelial ILC1 (iILC1) to produce IFN-γ and the proliferation of ILC1 and ILC3. Our study aims to evaluate the ex vivo effects of tofacitinib in RA patients and to investigate if ILC1s and ILC3s are specific targets of tofacitinib in RA.
METHODS:
Twenty RA patients starting tofacitinib and 10 RA patients starting anti-TNFα were enrolled. Peripheral blood mononuclear cells (PBMCs) from RA patients, collected before and three months after therapy, were cultured to evaluate ILC1 and ILC3 frequencies and the respective production of IFN-γ and IL-17 by flow cytometry analysis. PBMCs of RA patients were in vitro cultured with tofacitinib to evaluate the dose effects on ILC frequencies.
RESULTS:
RA patients showed a significant expansion of ILC1 but not ILC3. Unlike anti-TNFα treated patients, in whom no reduction in ILCs was reported, after three months of tofacitinib therapy the overall ILC frequency was reduced, as well as the ILC1 ability to release IFN-γ. In vitro treatment of PBMCs with tofacitinib demonstrated a dose-dependent reduction in the frequency of ILCs compared to untreated cells.
CONCLUSIONS:
Our preliminary results demonstrate that tofacitinib modulates the innate immune response by reducing the frequency of ILC1 cells and their production of IFN-γ.

DOI: https://doi.org/10.55563/clinexprheumatol/hhcnmt

Rheumatology Article