Macrophage phenotype in the subclinical gut inflammation of patients with ankylosing spondylitis.
OBJECTIVE
Long-term evolution of subclinical gut inflammation to overt Crohn's disease (CD) has been described in AS patients. The aim of this study was to evaluate macrophage polarization occurring in the inflamed gut of patients with AS.


METHODS
Twenty-seven HLA-B27(+) AS patients, 20 CD patients and 17 normal controls were consecutively enrolled. Classic M1 (iNOS(+)IL-10(-)), resolution phase (iNOS(+)IL-10(+)), M2 and CD14(+) macrophages were characterized by immunohistochemistry and flow cytometry. Quantitative gene expression analysis of IFN-γ, IL-4, IL-5, IL-33 and STAT6 was performed by real time PCR.


RESULTS
Classic M1 macrophages were expanded in CD and AS, where resolution phase macrophages predominate. A large increase in CD163(+) (M2) macrophages was observed in AS strictly correlated with the expression of IL-33, a Th2 cytokine involved in M2 polarization. Unlike in CD, CD14(+) macrophages were virtually absent in the gut of AS patients and controls.


CONCLUSIONS
The absence of CD14(+) macrophages together with the expansion of resolution phase and M2 macrophages is the immunological signature of subclinical ileal inflammation in AS.
Division of Rheumatology, Department of Internal Medicine, Piazza delle Cliniche 2, 90127 Palermo, Italy. giovanni.triolo@unipa.it.
Francesco
F
Ciccia
Riccardo
R
Alessandro
Aroldo
A
Rizzo
Antonina
A
Accardo-Palumbo
Stefania
S
Raimondo
Francesca
F
Raiata
Giuliana
G
Guggino
AnnaRita
A
Giardina
Giacomo
G
De Leo
Guido
G
Sireci
Giovanni
G
Triolo
D000328:Adult; D000368:Aged; D001706:Biopsy; D016207:Cytokines / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007079:Ileitis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D007082:Ileum / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D013167:Spondylitis, Ankylosing / Q000150:complications / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
D016207:Cytokines; D004247:DNA
M1 macrophages; M2 macrophages; ankylosing spondylitis; gut inflammation; interleukin 33; resolution phase macrophages