TY - JOUR
T1 - Proinflammatory CX3CR1+CD59+Tumor Necrosis Factor–Like Molecule 1A+Interleukin-23+ Monocytes Are Expanded in Patients With Ankylosing Spondylitis and Modulate Innate Lymphoid Cell 3 Immune Functions
AU - Ciccia, Francesco
AU - Guggino, Giuliana
AU - Zeng, Michael
AU - Thomas, Ranjeny
AU - Ranganathan, Vidya
AU - Rahman, Arifur
AU - Alessandro, Riccardo
AU - Rizzo, Aroldo
AU - Saieva, Laura
AU - Macaluso, Federica
AU - Peralta, Sergio
AU - di Liberto, Diana
AU - Dieli, Francesco
AU - Cipriani, Paola
AU - Giacomelli, Roberto
AU - Baeten, Dominique
AU - Haroon, Nigil
PY - 2018
Y1 - 2018
N2 - Objective: Gut-derived innate lymphoid cell 3 (ILC3) has been shown to participate in the pathogenesis of ankylosing spondylitis (AS). CX3CR1+ mononuclear phagocytes (MNPs) have been demonstrated to modulate ILC3 function in the gut. This study was undertaken to investigate the role of proinflammatory CX3CR1+CD59+ MNPs in modulating ILC3 function in AS patients. Methods: MNP subsets in the blood of AS patients and controls were analyzed by flow cytometry. The presence of CX3CR1+CD59+ cells in tissue was confirmed by confocal microscopy. Expression of the proinflammatory chemokines CX3CL1 and CCL2 and decoy receptor 6 (DcR-6) was analyzed. Peripheral CX3CR1+CD59+ cells were cocultured with ILC3, and changes in their frequency were evaluated by flow cytometry. Transcriptome analysis of circulating CX3CR1+ monocytes was also performed. Results: DcR-6 deficiency and CCL2 overexpression were observed in inflamed tissues from AS patients. In the gut, the proinflammatory CX3CR1+CD59+ MNP population was expanded, correlated with the presence of bacteria, and produced high levels of tumor necrosis factor–like molecule 1A (TL1A) and interleukin-23 (IL-23). MNPs positive for CD11b, CD11c, and major histocompatibility complex class II, predominantly expressing CX3CR1, were also expanded in the small intestines of treatment-naive SKG relative to BALB/c mice. The frequency of gut-derived CX3CR1+CD59+CCR9+TL1A+IL-23+ MNPs was significantly higher in the peripheral blood and synovial fluid of AS patients than controls. CCR9+CX3CR1+CD59+ monocytes were also expanded in AS synovial and bone marrow samples. Transcriptome analysis of isolated CX3CR1+CD59+ monocytes demonstrated a specific proinflammatory profile in AS. Isolated proinflammatory CX3CR1+CD59+ MNPs from AS patients induced the expansion and activation of ILC3. Conclusion: Proinflammatory CX3CR1+CD59+TL1A+IL-23+ MNPs are expanded in AS patients and display a specific proinflammatory transcriptome profile. Given the ability of these cells to support ILC3 expansion, they may promote a sustained proinflammatory status in AS.
AB - Objective: Gut-derived innate lymphoid cell 3 (ILC3) has been shown to participate in the pathogenesis of ankylosing spondylitis (AS). CX3CR1+ mononuclear phagocytes (MNPs) have been demonstrated to modulate ILC3 function in the gut. This study was undertaken to investigate the role of proinflammatory CX3CR1+CD59+ MNPs in modulating ILC3 function in AS patients. Methods: MNP subsets in the blood of AS patients and controls were analyzed by flow cytometry. The presence of CX3CR1+CD59+ cells in tissue was confirmed by confocal microscopy. Expression of the proinflammatory chemokines CX3CL1 and CCL2 and decoy receptor 6 (DcR-6) was analyzed. Peripheral CX3CR1+CD59+ cells were cocultured with ILC3, and changes in their frequency were evaluated by flow cytometry. Transcriptome analysis of circulating CX3CR1+ monocytes was also performed. Results: DcR-6 deficiency and CCL2 overexpression were observed in inflamed tissues from AS patients. In the gut, the proinflammatory CX3CR1+CD59+ MNP population was expanded, correlated with the presence of bacteria, and produced high levels of tumor necrosis factor–like molecule 1A (TL1A) and interleukin-23 (IL-23). MNPs positive for CD11b, CD11c, and major histocompatibility complex class II, predominantly expressing CX3CR1, were also expanded in the small intestines of treatment-naive SKG relative to BALB/c mice. The frequency of gut-derived CX3CR1+CD59+CCR9+TL1A+IL-23+ MNPs was significantly higher in the peripheral blood and synovial fluid of AS patients than controls. CCR9+CX3CR1+CD59+ monocytes were also expanded in AS synovial and bone marrow samples. Transcriptome analysis of isolated CX3CR1+CD59+ monocytes demonstrated a specific proinflammatory profile in AS. Isolated proinflammatory CX3CR1+CD59+ MNPs from AS patients induced the expansion and activation of ILC3. Conclusion: Proinflammatory CX3CR1+CD59+TL1A+IL-23+ MNPs are expanded in AS patients and display a specific proinflammatory transcriptome profile. Given the ability of these cells to support ILC3 expansion, they may promote a sustained proinflammatory status in AS.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85053897950&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29869839
U2 - https://doi.org/10.1002/art.40582
DO - https://doi.org/10.1002/art.40582
M3 - Article
C2 - 29869839
SN - 2326-5191
VL - 70
SP - 2003
EP - 2013
JO - Arthritis & rheumatology (Hoboken, N.J.)
JF - Arthritis & rheumatology (Hoboken, N.J.)
IS - 12
ER -