P Jaime1, N García-Guerrero2, R Estella3, J Pardo4, F García-Álvarez3, L Martinez-Lostao5. 1. Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón (ISS Aragón), Zaragoza, Spain; Centro de Investigación Biomédica de Aragón (CIBA), Instituto de Investigaciones Sanitarias de Aragón (ISS Aragon), Zaragoza, Spain. 2. Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón (ISS Aragón), Zaragoza, Spain. 3. Centro de Investigación Biomédica de Aragón (CIBA), Instituto de Investigaciones Sanitarias de Aragón (ISS Aragon), Zaragoza, Spain; Servicio de Cirugía Ortopédica y Traumatología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain. 4. Centro de Investigación Biomédica de Aragón (CIBA), Instituto de Investigaciones Sanitarias de Aragón (ISS Aragon), Zaragoza, Spain; Departamento de Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, Zaragoza, Spain; Instituto de Nanociencia de Aragón, IIS Aragón/Universidad de Zaragoza, Spain; Fundación Aragón I+D (ARAID), Gobierno de Aragón, Zaragoza, Spain. Electronic address: pardojim@unizar.es. 5. Instituto de Investigación Sanitaria de Aragón (ISS Aragón), Zaragoza, Spain; Departamento de Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, Zaragoza, Spain; Instituto de Nanociencia de Aragón, IIS Aragón/Universidad de Zaragoza, Spain; Servicio de Inmunología Hospital Clínico Universitario Lorenzo Blesa, Zaragoza, Spain. Electronic address: lumartin@unizar.es.
Abstract
OBJECTIVE: Natural killer (NK) cells have been involved in the pathology of different inflammatory and autoimmune disorders. Inflammation is an important regulator of osteoarthritis (OA), but the molecular and cellular mechanisms regulating this process are not well defined. DESIGN: To understand the role of NK cells in OA, we have compared the phenotype (CD56 subsets and perforin and granzyme expression) and cytotoxic function of NK cells in peripheral blood and synovial fluid from patients with OA undergoing total knee arthroplasty. RESULTS: In contrast to peripheral blood lymphocytes (PBLs), the majority of NK cells from the synovial fluid were CD56brightCD16(-) cells. As expected the expression of the cytolytic mediators perforin and granzyme B in CD56brightCD16(-) cells was low and correlated with a poor cytotoxic potential against K562 sensitive target cells. Surprisingly, this low cytotoxic NK cell subset expressed high levels of granzyme A (a protease recently characterized as a key modulator of inflammation in mouse models) in synovial fluid but not in peripheral blood. The presence of the CD56(+)brightCD16(-) cells expressing granzyme A correlated with increased levels of pro-inflammatory cytokines in synovial fluid from OA patients. CONCLUSION: Our results indicate that NK cells from the synovium of patients with OA, which present an immunoregulatory non-cytotoxic phenotype, show different phenotype comparing with NK cells from peripheral blood, especially expressing granzyme A, a pro-inflammatory molecule which may contribute to the establishment of chronic articular inflammation in this type of patients.
OBJECTIVE: Natural killer (NK) cells have been involved in the pathology of different inflammatory and autoimmune disorders. Inflammation is an important regulator of osteoarthritis (OA), but the molecular and cellular mechanisms regulating this process are not well defined. DESIGN: To understand the role of NK cells in OA, we have compared the phenotype (CD56 subsets and perforin and granzyme expression) and cytotoxic function of NK cells in peripheral blood and synovial fluid from patients with OA undergoing total knee arthroplasty. RESULTS: In contrast to peripheral blood lymphocytes (PBLs), the majority of NK cells from the synovial fluid were CD56brightCD16(-) cells. As expected the expression of the cytolytic mediators perforin and granzyme B in CD56brightCD16(-) cells was low and correlated with a poor cytotoxic potential against K562 sensitive target cells. Surprisingly, this low cytotoxic NK cell subset expressed high levels of granzyme A (a protease recently characterized as a key modulator of inflammation in mouse models) in synovial fluid but not in peripheral blood. The presence of the CD56(+)brightCD16(-) cells expressing granzyme A correlated with increased levels of pro-inflammatory cytokines in synovial fluid from OA patients. CONCLUSION: Our results indicate that NK cells from the synovium of patients with OA, which present an immunoregulatory non-cytotoxic phenotype, show different phenotype comparing with NK cells from peripheral blood, especially expressing granzyme A, a pro-inflammatory molecule which may contribute to the establishment of chronic articular inflammation in this type of patients.
Authors: Hilde Brouwers; Johannes Hendrick von Hegedus; Enrike van der Linden; Rachid Mahdad; Margreet Kloppenburg; René Toes; Martin Giera; Andreea Ioan-Facsinay Journal: Arthritis Res Ther Date: 2022-01-08 Impact factor: 5.156