About

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Research topics

• Medicine
• Internal medicine
• Pediatrics
• Dermatology
• Intensive care medicine
• Physical therapy

Selected publications

• Pathogenic role of MIF receptor (CD74) expressing T cells in inflammatory arthritis

  Proceedings of the National Academy of Sciences · 2026-01-08 · 2 citations

  articleOpen access

  High expression alleles of the innate cytokine, macrophage migration inhibitory factor (MIF), are associated with the development or the severity of autoimmune inflammatory diseases, including rheumatoid arthritis. Numerous studies support MIF's role in activating inflammatory pathways and MIF inhibition reduces joint pathology in different experimental models of arthritis. We examined the impact of gene deletion of MIF or its cognate receptor CD74 in the T cell-dependent model of collagen-induced arthritis (CIA) and observed the complete absence of arthritis development, suggesting an unforeseen role for MIF/CD74 signaling in the development of arthritogenic T cells. While MIF has been shown in model systems to contribute to T cell activation by augmenting innate responses, fewer than 1% of T lineage cells express CD74 in naive spleens and lymph nodes, and its functional consequences in pathogenic T cell subpopulations have not been studied. We found CD74+ T cells to expand during CIA and to increase in number within joint synovium, where they express an effector memory phenotype and recapitulate CIA development upon transfer into naive mice. We further found evidence for the presence of CD74+ T cells in the circulation and joint synovium of patients with rheumatoid arthritis. MIF-dependent, CD74+ T cells may contribute to the chronicity of rheumatoid synovitis and to disease relapse in previously inflamed joints.

  PublisherDOI

• Comorbid Rheumatic Conditions in the Treatment of Headache

  CRC Press eBooks · 2024

  Senior authorCorresponding
  • Medicine
  • Intensive care medicine
  • Dermatology

  This chapter provides a general overview of the most common rheumatic diseases that can be comorbid with headache disorders. Rheumatic diseases can affect any organ system in the body at any age and can evolve over time. The main categories of rheumatic diseases are inflammatory arthritides, connective tissue diseases, vasculitides, and noninflammatory pain syndromes, many of which can coexist with headache disorders. This chapter will explore the most common presenting symptoms of each condition that nonrheumatologists should identify as possibly related to an underlying rheumatological diagnosis. The most important aspects of the initial workup, diagnosis, and basic management for each condition will provide nonrheumatologists with a comprehensive understanding of each condition. By the end of the chapter, readers should be able to identify the signs and symptoms of the most common rheumatic diseases, understand the basic workup, and recognize when to refer to a rheumatologist for further management.

  PublisherDOI

• Global Rheumatology Research: Frontiers, Challenges, and Opportunities

  Arthritis & Rheumatology · 2021 · 21 citations

  1st authorCorresponding
  • Internal medicine
  • Medicine

  Rheumatologic and musculoskeletal diseases (RMDs) are important causes of morbidity and mortality worldwide. The World Health Organization (WHO) considers musculoskeletal conditions to be the leading cause of disability worldwide, and the greatest independent contributors to chronic pain. Population-based surveys from low- and middle-income countries (LMICs) have demonstrated similar rates of RMDs compared with high-income countries.

  PublisherOA PDFDOI

• Chikungunya: an emerging rheumatological pandemic?

  Current rheumatology research. · 2021-11-30 · 2 citations

  articleOpen access1st authorCorresponding

  species mosquitos and has spread beyond its endemic regions in East Africa and South Asia through the Indian Ocean islands, into Southern Europe, and through the Caribbean and the wider Americas. Acute chikungunya fever (CHIKF) is characterized by high fevers, arthralgias, myalgias, headaches, gastrointestinal disturbances, and maculopapular rash. Almost all patients recover from the acute illness, but up to fifty percent develop a chronic rheumatic syndrome with disabling arthritis that can last for months to years. Treatment of acute CHIKF is mainly supportive, while immunomodulation of chronic rheumatic disease with disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate appears to be beneficial. Preventive measures such as mosquito vector control and vaccination could decrease transmission and reduce the burden of chronic disabling post-viral arthritis.

  PublisherOA PDFDOI

• Transcriptomic analysis of human IL‐7 receptor alpha^low and^high effector memory CD8⁺ T cells reveals an age‐associated signature linked to influenza vaccine response in older adults

  Aging Cell · 2019-05-01 · 27 citations

  articleOpen access

  Abstract Here, we investigated the relationship of the age‐associated expansion of IL‐7 receptor alpha low (IL‐7Rα low ) effector memory (EM) CD8 + T cells with the global transcriptomic profile of peripheral blood cells in humans. We found 231 aging signature genes of IL‐7Rα low EM CD8 + T cells that corresponded to 15% of the age‐associated genes (231/1,497) reported by a meta‐analysis study on human peripheral whole blood from approximately 15,000 individuals, having high correlation with chronological age. These aging signature genes were the target genes of several transcription factors including MYC, SATB1, and BATF, which also belonged to the 231 genes, supporting the upstream regulatory role of these transcription factors in altering the gene expression profile of peripheral blood cells with aging. We validated the differential expression of these transcription factors between IL‐7Rα low and high EM CD8 + T cells as well as in peripheral blood mononuclear cells (PBMCs) of young and older adults. Finally, we found a significant association with influenza vaccine responses in older adults, suggesting the possible biological significance of the aging signature genes of IL‐7Rα low EM CD8 + T cells. The results of our study support the relationship of the expansion of IL‐7Rα low EM CD8 + T cells with the age‐associated changes in the gene expression profile of peripheral blood cells and its possible biological implications.

  PublisherOA PDFDOI

• Brief report: the disability of chronic chikungunya arthritis

  Clinical Rheumatology · 2019-04-08 · 19 citations

  articleOpen access
  PublisherOA PDFDOI

• Macrophage migration inhibitory factor (MIF) as a therapeutic target for rheumatoid arthritis and systemic lupus erythematosus

  Expert Opinion on Therapeutic Targets · 2019-08-15 · 166 citations

  reviewOpen access1st authorCorresponding

  Introduction. Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory cytokine with upstream regulatory roles in innate and adaptive immunity and is implicated in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Several classes of MIF inhibitors such as small molecule inhibitors and peptide inhibitors are in clinical development.Areas covered. The role of MIF in the pathogenesis of RA and SLE is examined; the authors review the structure, physiology and signaling characteristics of MIF and the related cytokine D-DT/MIF-2. The preclinical and clinical trial data for MIF inhibitors are also reviewed; information was retrieved from PubMed and ClinicalTrials.gov using the keywords MIF, D-DT/MIF-2, CD74, CD44, CXCR2, CXCR4, Jab-1, rheumatoid arthritis, systemic lupus erythematosus, MIF inhibitor, small molecule, anti-MIF, anti-CD74, and peptide inhibitor.Expert opinion. Studies in mice and in humans demonstrate the therapeutic potential of MIF inhibition for RA and SLE. MIF- directed approaches could be particularly efficacious in patients with high expression MIF genetic polymorphisms. In patients with RA and SLE and high expression MIF alleles, targeted MIF inhibition could be a precision medicine approach to treatment. Anti-MIF pharmacotherapies could also be steroid-sparing in patients with chronic glucocorticoid dependence or refractory autoimmune disease.

  PublisherOA PDFDOI

• Clinical Features and Management of Chronic Chikungunya Arthritis

  IntechOpen eBooks · 2019-06-27 · 2 citations

  book-chapterOpen access1st author

  Chikungunya virus is a single-stranded RNA alphavirus transmitted to humans by Aedes species mosquitos, causing an acute illness known as chikungunya fever with maculopapular rash, headache, polyarthritis/arthralgias, and gastrointestinal symptoms. Up to half of affected patients develop a chronic disabling arthritis following resolution of the acute infection, which can last for months or even years. The pathophysiology of chronic chikungunya arthritis remains controversial; it may result from a dysregulated immune response or be caused by persistent viral infection. Treatment for patients with chronic chikungunya arthritis remains investigational. Limited data suggests that immunosuppressive therapies such as methotrexate and TNF alpha inhibitors may be beneficial, though randomized clinical trials are needed.

  PublisherOA PDFDOI

• Transcriptomic analysis of human IL-7 receptor alphalow and higheffector memory CD8+ T cells reveals an age-associated signature linked to influenza vaccine response in older adults

  The Journal of Immunology · 2019-05-01 · 2 citations

  article

  Abstract Here we investigated the relationship of the age-associated expansion of IL-7 receptor alpha low (IL-7Rαlow) effector memory (EM) CD8+ T cells with the global transcriptomic profile of peripheral blood cells in humans. We found 231 aging signature genes of IL-7Rαlow EM CD8+T cells that corresponded to 15% of the age-associated genes (231/1,497) reported by a meta-analysis study on human peripheral whole blood from approximately 15,000 individuals, having high correlation with chronological age. These aging signature genes were the target genes of several transcription factors including MYC, SATB1, and BATF, which also belonged to the 231 genes, supporting the upstream regulatory role of these transcription factors in altering the gene expression profile of peripheral blood cells with aging. We validated the differential expression of these transcription factors between IL-7Rαlow and high EM CD8+ T cells as well as in peripheral blood mononuclear cells (PBMCs) of young and older adults. Finally, we found a significant association with influenza vaccine responses in older adults, suggesting the possible biological significance of the aging signature genes of IL-7Rαlow EM CD8+T cells. The results of our study support the relationship of the expansion of IL-7Rαlow EM CD8+ T cells with the age-associated changes in the gene expression profile of peripheral blood cells and its possible biological implications.

  PublisherDOI

• Chronic Chikungunya Arthritis and Rheumatoid Arthritis: What They Have in Common

  The American Journal of Medicine · 2019-11-06 · 126 citations

  reviewOpen access
  PublisherOA PDFDOI

Frequent coauthors

• Christiaan Scott

  Great Ormond Street Hospital for Children NHS Foundation Trust

  4 shared

• Xinping Tian

  Academy of Medical Sciences

  4 shared

• Evelyn Hsieh

  VA Connecticut Healthcare System

  4 shared

• Richard Bucala

  Yale University

  3 shared

• Robert T. Schoen

  3 shared

• J. Kennedy Amaral

  Universidade Federal do Cariri

  3 shared

• Laura B. Lewandowski

  National Institutes of Health

  2 shared

• Ingris Peláez‐Ballestas

  Hospital General de México

  2 shared

Education

• M.D.

  Vanderbilt University School of Medicine

• Other, Internal Medicine

  Yale-New Haven Hospital

  2016