The Role of FcγR Signaling in the K/B × N Serum Transfer Model of Arthritis

Neutrophils serve as a vanguard of the acute innate immune response to invading pathogens. Neutrophils are also abundant at sites of autoimmune inflammation, such as the rheumatoid joint, although their pathophysiologic role is incompletely defined and relevant effector functions remain obscure. Using genetic and pharmacologic approaches in the K/BxN serum transfer model of arthritis, we find that autoantibody-driven erosive synovitis is critically reliant on the generation of leukotrienes, and more specifically on leukotriene B4 (LTB4), for disease induction as well as perpetuation. Pursuing the cellular source for this mediator, we find via reconstitution experiments that mast cells are a dispensable source of leukotrienes, whereas arthritis susceptibility can be restored to leukotriene-deficient mice by intravenous administration of wild-type neutrophils. These experiments demonstrate a nonredundant role for LTB4 in inflammatory arthritis and define a neutrophil mediator involved in orchestrating the synovial eruption.

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G-Protein Receptor Kinases (grKs) Play an Important Regulatory Role in the K/BxN Serum Transfer Model of Inflammatory Arthritis

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2006.12.288 ◽

2007 ◽

Vol 119 (1) ◽

pp. S234-S235

Author(s):

T.K. Tarrant ◽

R.R. Rampersad ◽

C.G. Moore ◽

L.R. Rothlein ◽

R.M. Lefkowitz ◽

...

Keyword(s):

G Protein ◽

Inflammatory Arthritis ◽

Regulatory Role ◽

Transfer Model ◽

Protein Receptor ◽

Serum Transfer ◽

Receptor Kinases ◽

Serum Transfer Model

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Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients

Frontiers in Immunology ◽

10.3389/fimmu.2021.777792 ◽

2022 ◽

Vol 12 ◽

Author(s):

Thomas Weissmann ◽

Michael Rückert ◽

Jian-Guo Zhou ◽

Michaela Seeling ◽

Sebastian Lettmaier ◽

...

Keyword(s):

Mouse Model ◽

Molecular Mechanisms ◽

Low Dose ◽

Transfer Model ◽

Clinical Approach ◽

Analgesic Effects ◽

Low Dose Radiotherapy ◽

Serum Transfer ◽

Highly Effective ◽

Serum Transfer Model

Osteoarthritis (OA) is the leading degenerative joint disease in the western world and leads, if left untreated, to a progressive deterioration of joint functionality, ultimately reducing quality of life. Recent data has shown, that especially OA of the ankle and foot are among the most frequently affected regions. Current research in OA points towards a complex involvement of various cell and tissue types, often accompanied by inflammation. Low-dose radiotherapy (LDRT) is widely used for the treatment of degenerative and inflammatory diseases. While the reported analgesic effects are well known, the underlying molecular mechanisms are only poorly understood. We therefore correlated a clinical approach, looking at pain reduction in 196 patients treated with LDRT with a pre-clinical approach, utilizing the K/BxN serum transfer mouse model using flow cytometry and multiplex ELISA for analysis. While an improvement of symptoms in the majority of patients was found, patients suffering from symptoms within the tarsi transversa show a significantly lower level of improvement. Further, a significant impact of therapy success was detected depending on whether only one or both feet were affected. Further, patients of younger age showed a significantly better outcome than older ones while needing fewer treatment series. When looking on a cellular level within the mouse model, a systemic alteration of immune cells namely a shift from CD8+ to CD4+ T cells and reduced numbers of DCs was observed. A general reduction of inflammatory cytokines was detected, with significant alterations in IL-4 and IL-17 levels, all of which could potentially be responsible for the highly effective clinical improvement in patients. Taken together our data indicate that LDRT can be regarded as a highly effective treatment option for patients suffering from OA of the foot and ankle, in terms of analgesic effects, especially in younger patients. Furthermore, the observed effects are mediated by an interplay of cellular and soluble immune factors, as observed in the K/BxN serum transfer model. With this interdisciplinary approach we aim to encourage the usage of LDRT as an additive treatment strategy not only as a last resort, but also earlier in the course of disease.

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Gene targeting of properdin ameliorates disease development in the K/BxN mouse serum transfer model of arthritis

Molecular Immunology ◽

10.1016/j.molimm.2008.08.051 ◽

2008 ◽

Vol 45 (16) ◽

pp. 4112

Author(s):

Yuko Kimura ◽

Lin Zhou ◽

David Kim ◽

Takashi Miwa ◽

Wen-Chao Song

Keyword(s):

Gene Targeting ◽

Mouse Serum ◽

Transfer Model ◽

Disease Development ◽

Serum Transfer ◽

Serum Transfer Model

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Supporting Students in Using Energy Ideas to Interpret Phenomena: The Role of an Energy Representation

International Journal of Science and Mathematics Education ◽

10.1007/s10763-019-10035-y ◽

2019 ◽

Vol 18 (8) ◽

pp. 1635-1654

Author(s):

Marcus Kubsch ◽

Jeffrey Nordine ◽

David Fortus ◽

Joseph Krajcik ◽

Knut Neumann

Keyword(s):

Energy Transfer ◽

Qualitative Content Analysis ◽

Transfer Model ◽

School Students ◽

Making Sense ◽

8Th Grade ◽

Quasi Experimental ◽

Important Idea ◽

Support Students

AbstractIn the sciences, energy is an important idea to get insight into phenomena, as energy can help to reveal hidden systems and processes. However, students commonly struggle to use energy ideas to interpret and explain phenomena. To support students in using energy ideas to interpret and explain phenomena, a range of different graphical representations are commonly used. However, there is little empirical research regarding whether and how these representations actually support students’ ability to use energy ideas. Building on common ways of representing energy transfer, we address this issue by exploring whether, and if so how, a specific representation called the energy transfer model (ETM) supports middle school students’ interpretation of phenomena using the idea of energy transfer. We conducted an interview study with N = 30 8th grade students in a quasi-experimental setting and used qualitative content analysis to investigate student answers. We found evidence that students who construct an ETM when making sense of phenomena consider the role of energy transfers between systems more comprehensively, i.e., they reason about hidden processes and systems to a larger extent than students who do not construct an ETM.

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Extracellular adenosine regulates colitis through effects on lymphoid and nonlymphoid cells

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00404.2013 ◽

2014 ◽

Vol 307 (3) ◽

pp. G338-G346 ◽

Cited By ~ 16

Author(s):

Courtney C. Kurtz ◽

Ioannis Drygiannakis ◽

Makoto Naganuma ◽

Sanford Feldman ◽

Vasileios Bekiaris ◽

...

Keyword(s):

Adoptive Transfer ◽

Inflammatory Responses ◽

Severe Disease ◽

T Cell Subsets ◽

Transfer Model ◽

Wild Type ◽

Colonic Inflammation ◽

Th Cells ◽

Extracellular Adenosine

Adenosine is a purine metabolite that can mediate anti-inflammatory responses in the digestive tract through the A2A adenosine receptor (A2AAR). We examined the role of this receptor in the control of inflammation in the adoptive transfer model of colitis. Infection of A2AAR−/− mice with Helicobacter hepaticus increased colonic inflammation scores compared with uninfected A2AAR controls. Comparison of T cell subsets in wild-type and A2AAR−/− mice revealed differences in markers associated with activated helper T (Th) cells and regulatory T (Treg) cells. Previous studies showed that expression of A2AAR on CD45RBHI and CD45RBLO Th cells is essential for the proper regulation of colonic inflammation. Adoptive transfer of CD45RBHI with CD45RBLO from wild-type mice into RAG1−/−/A2AAR−/− mice induced severe disease within 3 wk, although transfer of the same subsets into RAG1−/− mice does not induce colitis. This suggests that the presence of A2AAR on recipient cells is also important for controlling colitis. To investigate the role of A2AAR in myeloid cells, chimeric recipients were generated by injection of bone marrow from RAG1−/− or RAG1−/−/A2AAR−/− mice into irradiated RAG1−/− mice. After adoptive transfer, these recipients did not develop colitis, regardless of A2AAR expression by the donor. Together, our results suggest that the control of inflammation in vivo is dependent on A2AAR signaling through multiple cell types that collaborate in the regulation of colitis by responding to extracellular adenosine.

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IL-27 promotes T cell–dependent colitis through multiple mechanisms

Journal of Experimental Medicine ◽

10.1084/jem.20100410 ◽

2010 ◽

Vol 208 (1) ◽

pp. 115-123 ◽

Cited By ~ 86

Author(s):

Jennifer H. Cox ◽

Noelyn M. Kljavin ◽

Nandhini Ramamoorthi ◽

Lauri Diehl ◽

Marcel Batten ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Intestinal Inflammation ◽

Interferon Γ ◽

Transfer Model ◽

Proinflammatory Role ◽

Immune Pathology

Interleukin-27 (IL-27) is a cytokine known to have both proinflammatory and immunoregulatory functions. The latter appear to dominate in vivo, where IL-27 suppresses TH17 responses and promotes the differentiation of Tr1 cells expressing interferon-γ and IL-10 and lacking forkhead box P3 (Foxp3). Accordingly, IL-27 receptor α (Il27ra)–deficient mice suffer from exacerbated immune pathology when infected with various parasites or challenged with autoantigens. Because the role of IL-27 in human and experimental mouse colitis is controversial, we studied the consequences of Il27ra deletion in the mouse T cell transfer model of colitis and unexpectedly discovered a proinflammatory role of IL-27. Absence of Il27ra on transferred T cells resulted in diminished weight loss and reduced colonic inflammation. A greater fraction of transferred T cells assumed a Foxp3+ phenotype in the absence of Il27ra, suggesting that IL-27 functions to restrain regulatory T cell (Treg) development. Indeed, IL-27 suppressed Foxp3 induction in vitro and in an ovalbumin-dependent tolerization model in vivo. Furthermore, effector cell proliferation and IFN-γ production were reduced in the absence of Il27ra. Collectively, we describe a proinflammatory role of IL-27 in T cell–dependent intestinal inflammation and provide a rationale for targeting this cytokine in pathological situations that result from a breakdown in peripheral immune tolerance.

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