Approaches to Establishing Tolerance in Immune Mediated Diseases

Huffaker, Michelle F.; Sanda, Srinath; Chandran, Sindhu; Chung, Sharon A.; Clair, E. William St.; Nepom, Gerald T.; Smilek, Dawn E.

doi:10.3389/fimmu.2021.744804

Cited by 9 publications

(9 citation statements)

References 76 publications

(76 reference statements)

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“…M1 macrophages increased slightly after several injections. Immune tolerance may play a role in this phenomenon [ 20 ], for we also found a phenomenon that if the first two injections were not effective, the follow-up effect was also not good.…”

Section: Discussionmentioning

confidence: 92%

Effect of hyaluronic acid on cytokines and immune cells change in patients of knee osteoarthritis

Jin

Liang

et al. 2022

BMC Musculoskelet Disord

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Purpose To evaluate the changes of cytokines and immune cells after Intra-articular hyaluronic acid(IAHA)injections in patients with knee osteoarthritis (KOA). Patients and Methods Sixteen patients were included in the study, with a total of 65 IAHA injections. The Numeric Rating Scale (NRS) and Lysholm scores were evaluated at each visit. The immune cells and 14 cytokines of synovial fluid were analyzed at each visit. The association between immune cells and cytokines were examined. Results IL-6 and IL-8 were the most common cytokines in the synovial fluid of KOA patients. The synovial fluid was orchestrated by macrophages (69%) and Lymphocytes (18%). Neutrophils were less to count of the total cell population (< 2%). The cytokines decreased significantly after the first injection and then tended to be stable. Lymphocytes increased a lot, while Macrophages decreased in the early stage, then increased after multiple injections. The proposition of M1 decreased in the early stage, then increased after multiple injections, while M2 increased consistently. M1 and M2 were positively associated with IL-6 and IL-8. Conclusion The synovial fluid of KOA patients was orchestrated by macrophages (69%) and Lymphocytes (18%) and cytokines like IL-6 and IL-8. IAHA may play an anti-inflammatory functional role through the decreased production of IL-6 and IL-8 by macrophages through polarization. The results from this study partially revealed the effect of IAHA on cytokines and immune cells change in KOA patients, and therapies targeting pathogenic cytokines and immune cells might be used to attenuate the knee joint inflammation and release pain. Trial registration ChiCTR2100050133; date registered 17 August 2021.

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Section: Discussionmentioning

confidence: 92%

Effect of hyaluronic acid on cytokines and immune cells change in patients of knee osteoarthritis

Jin

Liang

et al. 2022

BMC Musculoskelet Disord

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Section: Discussionmentioning

confidence: 99%

“…In this manuscript, we explore new mechanisms by which the immune response against a particular antigen, such as collagen, can be downregulated [ 4 ]. Tolerance of self-antigens prevents potentially harmful immune responses against the body’s own proteins, through anergy, deletion, or development of induced Tregs [ 4 ]. These regulatory immune cells circulate throughout the body to maintain tolerance, and are important for turning an immune response off after a problem is resolved.…”

Section: Discussionmentioning

confidence: 99%

“…When extracted, purified, and administered systemically, both human and murine studies have shown that it attenuates autoimmune arthritis [ 2 , 3 ]. This suppression is partly due to the induction of immune tolerance, which is the prevention of an immune response against a particular antigen, by anergy, deletion, or induced Tregs [ 4 ]. Another mechanism which has been less explored is the activation of the inhibitory receptor Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Role of Citrullinated Collagen in Autoimmune Arthritis

Myers

Ouyang

Patel

et al. 2022

IJMS

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Citrullination of proteins plays an important role in protein function and it has recently become clear that citrullinated proteins play a role in immune responses. In this study we examined how citrullinated collagen, an extracellular matrix protein, affects T-cell function during the development of autoimmune arthritis. Using an HLA-DR1 transgenic mouse model of rheumatoid arthritis, mice were treated intraperitoneally with either native type I collagen (CI), citrullinated CI (cit-CI), or phosphate buffered saline (PBS) prior to induction of autoimmune arthritis. While the mice given native CI had significantly less severe arthritis than controls administered PBS, mice receiving cit-CI had no decrease in the severity of autoimmune arthritis. Using Jurkat cells expressing the inhibitory receptor leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), Western blot analysis indicated that while CI and cit-CI bound to LAIR-1 with similar affinity, only CI induced phosphorylation of the LAIR ITIM tyrosines; cit-CI was ineffective. These data suggest that cit-CI acts as an antagonist of LAIR-1 signaling, and that the severity of autoimmune arthritis can effectively be altered by targeting T cells with citrullinated collagen.

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“…As outlined in a recent review of multiple studies from the Immune Tolerance Network (27), using a mechanistic approach to classify therapeutic intervention in immune-mediated diseases into (i) interrupting effector mechanisms, (ii) restraining innate activation, or (iii) boosting regulation, presents an opportunity to address challenges posed by persistent immunologic memory and deficient immunologic regulation in diverse clinical contexts. It is now timely to translate these mechanism-focused observations into practicable therapeutic strategy.…”

Section: Discussionmentioning

confidence: 99%

Approaches to Establishing Tolerance in Immune Mediated Diseases

Cited by 9 publications

References 76 publications

Effect of hyaluronic acid on cytokines and immune cells change in patients of knee osteoarthritis

Effect of hyaluronic acid on cytokines and immune cells change in patients of knee osteoarthritis

Role of Citrullinated Collagen in Autoimmune Arthritis

Synergistic targeting of immunologic pathways to empower durable tolerance therapies

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