- Chemokines beyond chemo-attraction: CXCL10 and its significant role in cancer and autoimmunity. [Journal Article]
- CCytokine 2018 Feb 12
- Chemokines are mostly known for their chemotactic properties, and less for their ability to direct the biological function of target cells, including T cells. The current review focuses on a key chem...
Chemokines are mostly known for their chemotactic properties, and less for their ability to direct the biological function of target cells, including T cells. The current review focuses on a key chemokine named CXCL10 and its role in directing the migratory propertied and biological function of CD4+ and CD8+ T cells in the context of cancer and inflammatory autoimmunity. CXCR3 is a chemokine receptor that is abundant on CD4+ T cells, CD8+ T cells and NK cells. It has three known ligands: CXCL9, CXCL10 and CXCL11. Different studies, including those coming form our laboratory, indicated that aside of attracting CD8+ and CD4+ effector T cells to tumor sites and sites of inflammation CXCL10 directs the polarization and potentiates the biological function of these cells. This makes CXCL10 a "key driver chemokine" and a valid target for therapy of autoimmune diseases such as Inflammatory Bowl's Disease, Multiple Sclerosis, Rheumatoid arthritis and others. As for cancer this motivated different groups, including our group to develop CXCL10 based therapies for cancer due to its ability to enhance T-dependent anti cancer immunity. The current review summarizes these findings and their potential translational implication.
- The RORγt-CCR6-CCL20 axis augments Th17 cells invasion into the synovia of rheumatoid arthritis patients. [Journal Article]
- MRMod Rheumatol 2018 Jan 22; :1-12
- CONCLUSIONS: The high expression of RORγt might facilitate the migration of Th17 cells to inflamed joints via the enhanced expression of CCR6 and contribute to the pathology of RA.
- Streptococcal tonsillitis related reactive arthritis - clinical, ultrasound imaging and immunohistochemical study. [Journal Article]
- RJRom J Morphol Embryol 2017; 58(3):801-807
- In clinical practice and literature studies, the most common condition associated to streptococcal tonsillitis used to be acute rheumatic fever (ARF). Several publications in the late years report a ...
In clinical practice and literature studies, the most common condition associated to streptococcal tonsillitis used to be acute rheumatic fever (ARF). Several publications in the late years report a more frequent and distinctive entity from ARF following β-hemolytic group A streptococcus infection in patients with post-infectious arthritis, that do not fulfill the modified Jones criteria, the so-called post-streptococcal reactive arthritis (PSRA). A distinctive pattern of clinical framing and biological profile in patients with PSRA following streptococcal tonsillitis is described, with a non-migratory, additive, recent onset (7-10 days) arthritis that affects small and large joints as well, with a bimodal peak of incidence at 8-14 and 21-37 years of age, with variate response to non-steroidal anti-inflammatory drugs and has a tendency for recurrence and persistence. Sacroiliitis, although rare, is described in human leukocyte antigen (HLA)-B27 positive PSRA patients. The main objective of the current study was to evaluate various immunohistochemical patterns of streptococcal tonsillitis in patients with PSRA and find possible correlations with the clinical, biological and ultrasound profile.
- Colon adenocarcinoma after jejunoileal bypass for morbid obesity. [Journal Article]
- JSJ Surg Case Rep 2017; 2017(11):rjx214
- Jejunoileal bypass (JIB) was developed as a surgical treatment for morbid obesity in the early 1950s. However, this procedure is now known to be associated with multiple metabolic complications and h...
Jejunoileal bypass (JIB) was developed as a surgical treatment for morbid obesity in the early 1950s. However, this procedure is now known to be associated with multiple metabolic complications and has subsequently been abandoned as a viable bariatric procedure. Some of these known complications include renal stone formation, liver failure, migratory arthritis, fat-soluble deficiencies, blind-loop syndrome and severe diarrhea. Additionally, there have been animal models suggesting colon dysplasia after JIB. To our knowledge however, in humans, no colon cancers have been attributed to JIB in the literature. Here we report a 63-year-old morbidly obese female who had a JIB surgery in 1973 and subsequently was found to have numerous sessile colonic polyps throughout her colon and adenocarcinoma of the ascending colon without any family history of colonic polyposis syndromes or colon cancer.
- SAPHO syndrome associated with hidradenitis suppurativa and pyoderma gangrenosum successfully treated with adalimumab and methotrexate: a case report and review of the literature. [Review]
- IJInt J Dermatol 2018; 57(1):10-18
- SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare inflammatory condition describing the combination of skin, bone, and joint manifestations that has a heterogeneous p...
SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare inflammatory condition describing the combination of skin, bone, and joint manifestations that has a heterogeneous presentation. We report a case of severe SAPHO syndrome in association with hidradenitis suppurativa and pyoderma gangrenosum in a 27-year-old male. The patient had an initial migratory arthritis affecting the knees, ankles, metacarpophalangeal joints, proximal interphalangeal joints, wrists, shoulder, and lower back, which progressed to a persistent arthritis and swelling at the sternum, shoulders, wrists, hands, feet, and lower back. Radiographic changes were consistent with the diagnosis of SAPHO syndrome. Serum proinflammatory cytokine levels were significantly elevated and improved substantially after 3 months of therapy. Rationale for therapy in this patient was the observation that tumor necrosis alpha antagonists have been successfully used in SAPHO syndrome, and since arthropathy was so prominent in our patient, we elected to use adalimumab combined with methotrexate.
- NF-κB2 Controls the Migratory Activity of Memory T Cells by Regulating Expression of CXCR4 in a Mouse Model of Sjögren's Syndrome. [Journal Article]
- ARArthritis Rheumatol 2017; 69(11):2193-2202
- CONCLUSIONS: Our results suggest that the RelB/NF-κB2 pathway regulates T cell migration to autoimmune targets through TGFβ/TGFβR-dependent regulation of CXCL12/CXCR4 signaling. This suggests that these signaling pathways are potential therapeutic targets for the treatment of autoimmune diseases.
- TNFα and IL-1β in the synovial fluid facilitate mucosal-associated invariant T (MAIT) cell migration. [Journal Article]
- CCytokine 2017; 99:91-98
- Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affect the joints and inflammatory cell migration into inflamed articular sites contribute to this disease. Among...
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affect the joints and inflammatory cell migration into inflamed articular sites contribute to this disease. Among the inflammatory cells, human mucosal-associated invariant T (MAIT) cells were recently recognized as critical cellular component with a pathological role in RA. However, their migratory characteristics are poorly understood. The aim of this study was to determine whether human MAIT cells preferentially traffick to inflamed synovial sites in rheumatoid arthritis patients and to elucidate the underlying mechanism. First, we found that TNFα and IL-1β were elevated in synovial fluid (SF) of RA patients, which resulted in increased expression of E-selectin, ICAM-1 and V-CAM-1 on blood vessel endothelial cells. To understand whether TNFα and IL-1β in the SF facilitated MAIT cell migration, we analyzed CD161+TCRα7.2+MAIT and other CD3+T cells for differences in migratory capacity. Collectively, our results demonstrate that TNFα and IL-1β in the SF facilitated MAIT cell migration dependent on expression of selectin ligand, sialyl LewisX(sLeX) and CCR6 on MAIT cells. We also showed that MAIT cells in the SF from RA patients equipped upregulated sLeXcompared to the peripheral blood of RA patients and healthy persons, which suggest that TNFα and IL-1β mediated expression of E-selectin preferentially attract sLeXmediated MAIT cell migration into the SF of RA patients.
- Chemokine signals are crucial for enhanced homing and differentiation of circulating osteoclast progenitor cells. [Journal Article]
- ARArthritis Res Ther 2017 Jun 15; 19(1):142
- CONCLUSIONS: In our study, we identified distinct effects of selected chemokines on stimulation of OCP mobilization, tissue homing, and maturation. Novel insights into migratory behaviors and functional properties of circulatory OCPs in response to chemotactic signals could open ways to new therapeutic targets in RA.
- Cellular and molecular pathways of structural damage in rheumatoid arthritis. [Review]
- SISemin Immunopathol 2017; 39(4):355-363
- Structural damage of cartilage and bone tissue is a hallmark of rheumatoid arthritis (RA). The resulting joint destruction constitutes one of the major disease consequences for patients and creates a...
Structural damage of cartilage and bone tissue is a hallmark of rheumatoid arthritis (RA). The resulting joint destruction constitutes one of the major disease consequences for patients and creates a significant burden for the society. The main cells executing bone and cartilage degradation are osteoclasts and fibroblast-like synoviocytes, respectively. The function of both cell types is heavily influenced by the immune system. In the last decades, research has identified several mediators of structural damage, ranging from infiltrating immune cells and inflammatory cytokines to autoantibodies. These factors result in an inflammatory milieu in the affected joints which leads to an increased development and function of osteoclasts and the transformation of fibroblast-like synoviocytes towards a highly migratory and destructive phenotype. In addition, repair mechanisms mediated by osteoblasts and chondrocytes are strongly impaired by the presence of pro-inflammatory cytokines. This article will review the current knowledge on the mechanisms of joint inflammation and the destruction of bone and cartilage.
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- Atypical Articular Presentations in Indian Children With Rheumatic Fever. [Journal Article]
- HLHeart Lung Circ 2018; 27(2):199-204
- CONCLUSIONS: Atypical manifestations in ARF may well be mistaken for a connective tissue disorder, post streptococcal reactive arthritis and septic arthritis. Physicians should be made aware of these features to prevent diagnostic dilemma, and to effect institution of appropriate management including penicillin prophylaxis.