Synovial fluid neutrophils transcribe and express class II major histocompatibility complex molecules in rheumatoid arthritis

Cross, Andrew; Bucknall, R C; Cassatella, Marco A.; Edwards, Steven W.; Moots, Robert J.

doi:10.1002/art.11253

Cited by 107 publications

(102 citation statements)

References 75 publications

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“…Because class II MHC is required for antigen presentation and T cell stimulation, enhanced expression of class II MHC would lead to enhanced T cell activation and subsequent cellactivation events in the joints of mice that received circulating fibrocytes. Notably, neutrophils derived from the synovial fluid of patients with RA express class II MHC (39).…”

Section: Discussionmentioning

confidence: 99%

Circulating fibrocytes contribute to the pathogenesis of collagen antibody–induced arthritis

Galligan¹,

Fish²

2012

Arthritis & Rheumatism

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Objective. Rheumatoid arthritis (RA) is a systemic autoimmune disease resulting in joint inflammation. Fibroblast-like synoviocytes in affected joints are responsible for pannus formation and cytokine/ chemokine production, resulting in leukocyte recruitment and bone/cartilage destruction. Previously, we identified a multipotent stem cell population of activated fibrocytes in the blood of patients with RA that may have a role in disease pathogenesis, perhaps as fibroblast-like synoviocyte precursors. The aim of this study was to further characterize the contribution of circulating fibrocytes to the pathogenesis of RA.Methods. Circulating fibrocytes were isolated from mice with collagen-induced arthritis and transferred intravenously into recipient mice with collagen antibody-induced arthritis (CAIA). The activation status of circulating fibrocytes was determined using multidimensional phosphoflow cytometric analysis of the signaling effectors STAT-5, STAT-1, AKT, and JNK. Circulating fibrocyte trafficking and matrix metalloproteinase (MMP) activity were assessed in real time using fluorescence molecular tomography, specifically labeling circulating fibrocytes with CellVue Maroon and measuring MMP activity using MMPSense 680.Results. The numbers of circulating fibrocytes were increased early during the onset of CAIA, concomitant with their activation, as measured by phosphorylation of STAT-5. Adoptive transfer of circulating fibrocytes augmented disease scores and increased class II major histocompatibility complex expression and peripheral blood phosphoactivation profiles in recipient mice with CAIA. Notably, adoptively transferred fluorescence-labeled circulating fibrocytes rapidly migrated into the affected joints of recipient mice with CAIA, and this was associated with augmented neutrophil recruitment into affected joints and MMP activation.Conclusion. Circulating fibrocytes migrate to joints and influence the onset of disease processes in arthritis.

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Section: Discussionmentioning

confidence: 99%

Circulating fibrocytes contribute to the pathogenesis of collagen antibody–induced arthritis

Galligan¹,

Fish²

2012

Arthritis & Rheumatism

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“…Although still expressing the usual neutrophil cell surface markers CD32, CD18 and CD11b, they acquired new surface proteins, such as HLA-DR and the co-stimulation molecule CD80, which are associated with antigen presentation. We note a similar instance of inflammatory Functions of long-lived neutrophilsreprogramming in synovial fluid neutrophils, a percentage of which expressed functional HLA-DR. 50 Neutrophils from patients with vasculitis and systemic bacterial infections also acquire novel surface receptors and functions, such as expression of CD64, CD14 and neoexpression of HLA-DR and CD83. 51,52 In addition, we showed that, relative to freshly isolated neutrophils, long-lived neutrophils have increased cell surface ICAM-1, neoexpression of CD49d with concomitant diminution in expression of the traditional neutrophil adhesion integrins b 1 and b 2 .…”

Section: Discussionmentioning

confidence: 99%

Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines

Chakravarti

Rusu

Flamand

et al. 2009

Laboratory Investigation

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Essential cells of innate immunity, neutrophils are often considered to be a homogenous population of terminally differentiated cells. During inflammation, neutrophils are extravasated cells exposed to local factors that prolong their survival and activate their production of mediators implicated in disease progression. In this study, a phenotypically distinct subset of human neutrophils that appear after prolonged exposure to cytokines was characterized. Freshly isolated neutrophils from healthy donors were incubated with granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-a and interleukin (IL)-4, three cytokines that are locally present in various inflammatory conditions. Eight to 17% of neutrophils survived beyond 72 h. This subset of non-apoptotic neutrophils, as evaluated by three different markers, was enriched by discontinuous Percoll gradient centrifugation before studying their phenotype. These viable neutrophils showed neoexpression of HLA-DR, CD80 and CD49d. Compared with freshly isolated neutrophils, they responded differentially to second signals similar to formyl-methionyl-leucyl-phenylalanine with three-to four-fold increases in production of superoxide anions and leukotrienes. These cells augmented their phagocytic index by 141%, increased their adhesion to human primary fibroblasts, but reduced their migration in response to chemotactic stimuli and decreased exocytosis of primary and secondary granules. In addition, they produced substantial amounts of IL-8, IL-1Ra and IL-1b. This neutrophil subset had a unique profile of phosphorylation of intracellular signaling molecules. In conclusion, the present identification of a novel neutrophil phenotype highlights the reprogammable character of the neutrophil. This aspect is crucial for our understanding of its contribution to disease pathogenesis and host defense.

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“…It can be speculated that even though neutrophils may be less potent than DCs in processing and presenting antigenic peptides to T cells and be less relevant for the induction of primary T cell responses in the draining lymph nodes, the sheer quantity of neutrophils rapidly recruited to the site of infection will easily outnumber local DCs that are relatively sparse in peripheral tissues. Indirect evidence for the existence of APC-like neutrophils comes from studies in patients with various infectious and non-infectious inflammatory diseases [90][91][92][93][94][95][96], most notably in acute sepsis where circulating neutrophils possess a phenotype similar to Vc9/Vd2 T cell-primed neutrophils and are similarly capable of cross-presenting soluble proteins to antigen-specific CD8 + T cells [10]. These findings support the existence of an effective sentinel network comprised of Vc9/Vd2 T cells and their crosstalk with neighboring immune and non-immune cells [4], and identify a novel role for human unconventional T cells in shaping the transition of the innate to the adaptive phase of anti-microbial responses.…”

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confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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a b s t r a c tUnconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vc9/Vd2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vc9/Vd2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines.Ó 2015 Published by Elsevier Inc. Introduction cd T cells represent a third lineage of lymphocytes expressingre-arranged antigen receptors that co-evolved with 'classical' B cells and ab T cells over 400 million years, arguing for a crucial and non-redundant contribution of each lymphocyte to effective immune responses, and hence the evolutionary survival of all jawed vertebrate species [1]. 30 years have passed since the accidental and unexpected cloning of the cd T cell receptor (TCR) and the subsequent realization that ab T cells and cd T cells are fundamentally different with respect to the types of antigens they recognize and the distinct effector functions triggered upon such recognition. However, the manifold contributions of cd T cells to homeostasis, inflammation, infection and tumor surveillance have historically been neglected and are only beginning to be integrated into comprehensive models of the immune system [1][2][3][4][5][6][7].1. Innate-like pattern recognition by human Vc9/Vd2 T cells Like other 'unconventional' T cells carrying an ab TCR such as mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells, cd T cells are characterized by a markedly restrictedTCR usage that allows them to recognize self and non-self molecules in the absence of classical antigen presentation via MHC I or MHC II. Vc9/Vd2 + cd T cells represent the major cd T cell subset in human peripheral blood where they typically comprise 1-5% in healthy adults [8]. In many microbial infections, Vc9/Vd2 T cells increase locally and/or systemically [9,10] and can reach in excess of 50% of all peripheral T cells within a matter of days [11], revealing a fundamental role of this unconventional T cell population in acute disease and suggesting their exploitation for diagnostic and therapeutic purposes [12][13][14]. Vc9/Vd2 T cells uniformly respond to a class of low molecular weight molecules often referred to as 'phosphoantigens' that represent metabolites of the isoprenoid biosynthesis...

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Synovial fluid neutrophils transcribe and express class II major histocompatibility complex molecules in rheumatoid arthritis

Cited by 107 publications

References 75 publications

Circulating fibrocytes contribute to the pathogenesis of collagen antibody–induced arthritis

Circulating fibrocytes contribute to the pathogenesis of collagen antibody–induced arthritis

Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

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