Interleukin (IL)-22 receptor 1 is over-expressed in primary Sjogren's syndrome and Sjögren-associated non-Hodgkin lymphomas and is regulated by IL-18
Copyright policy )Interleukin (IL)-22 receptor 1 is over-expressed in primary Sjogren's syndrome and Sjögren-associated non-Hodgkin lymphomas and is regulated by IL-18
Summary The aim of this study was to elucidate more clearly the role of interleukin (IL)-18 in modulating the IL-22 pathway in primary Sjögren's syndrome (pSS) patients and in pSS-associated lymphomas. Minor salivary glands (MSGs) from patients with pSS and non-specific chronic sialoadenitis (nSCS), parotid glands biopsies from non-Hodgkin lymphomas (NHL) developed in pSS patients, were evaluated for IL-18, IL-22, IL-22 receptor 1 (IL-22R1), IL-22 binding protein (IL-22BP) and signal transducer and activator of transcription-3 (STAT-3) expression. MSGs IL-22R1-expressing cells were characterized by confocal microscopy and flow cytometry in pSS, nSCS and healthy controls. The effect of recombinant IL-18 and IL-22 on peripheral blood mononuclear cells (PBMCs) from pSS and nSCS was studied by flow cytometry and reverse transcription–polymerase chain reaction (RT-PCR). MSGs of pSS and NHL were characterized by an imbalance between IL-22 and IL-22BP protein expression, with IL-18 and IL-22BP being expressed in a mutually exclusive manner and IL-18 and IL-22R1 being correlated directly. Aberrant expression of IL-22R1, induced by IL-18, was observed only among tissue and circulating myeloid cells of pSS patients and macrophages of NHL tissues of pSS patients, but not nSCS. IL-22R1 expression on PBMC of pSS was functional, as its stimulation with recombinant IL-22 significantly up-regulated the expression of STAT-3, IL-17 and IL-22. An IL-18-dependent aberrant expression of IL-22R1 on cells of haematopoietic origin seems to be a specific immunological signature of patients with pSS and pSS-associated lymphomas.
- Queen Mary University of London United Kingdom
- University of L'Aquila Italy
- University of Palermo Italy
- William Harvey Research Institute United Kingdom
- Ospedale Vincenzo Cervello Italy
Adult, Male, STAT3 Transcription Factor, Interleukins, Lymphoma, Non-Hodgkin, Macrophages, Interleukin-17, Primary Cell Culture, Interleukin-18, Lacrimal Apparatus, Receptors, Interleukin, Middle Aged, Salivary Glands, Sialadenitis, Gene Expression Regulation, IL-18; IL-22; IL-22BP; IL-22R1; Sjögren's syndrome; non-Hodgkin lymphoma, Leukocytes, Mononuclear, Humans, Female, Myeloid Cells, Aged
Adult, Male, STAT3 Transcription Factor, Interleukins, Lymphoma, Non-Hodgkin, Macrophages, Interleukin-17, Primary Cell Culture, Interleukin-18, Lacrimal Apparatus, Receptors, Interleukin, Middle Aged, Salivary Glands, Sialadenitis, Gene Expression Regulation, IL-18; IL-22; IL-22BP; IL-22R1; Sjögren's syndrome; non-Hodgkin lymphoma, Leukocytes, Mononuclear, Humans, Female, Myeloid Cells, Aged
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