RESUMO
B lymphocyte stimulator (BLyS), a tumor neurosis factor ligand superfamily, is an important factor of B cell survival and activation. However, BLyS also regulates T cell activation and survival, playing key roles in T cell-mediated autoimmune disorders. In the paper, we introduced the mechanisms of BLyS and a proliferation-inducing ligand (APRIL) regulating T cell responses and their roles in rheumatoid arthritis (RA).
Assuntos
Animais , Humanos , Anticorpos Monoclonais Humanizados , Usos Terapêuticos , Artrite Reumatoide , Tratamento Farmacológico , Metabolismo , Patologia , Fator Ativador de Células B , Metabolismo , Receptor do Fator Ativador de Células B , Metabolismo , Antígeno de Maturação de Linfócitos B , Metabolismo , Linfócitos B , Metabolismo , Patologia , Ativação Linfocitária , Proteínas Recombinantes de Fusão , Usos Terapêuticos , Linfócitos T , Metabolismo , Patologia , Proteína Transmembrana Ativadora e Interagente do CAML , Metabolismo , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral , MetabolismoRESUMO
Asthma was induced by the sensitization and challenge with ovalbumin (OVA) in mice. B-cell activating factor (BAFF) plays a role in mature B cell generation and maintenance. Here, we investigated whether, BAFF expression was changed in OVA-induced mice and whether the control of BAFF expression level alleviates the symptom of bronchial asthma. BAFF expression was detected in alveolar-associated cells surrounding bronchi of OVA-induced mouse lung tissues. BAFF protein was also increased in OVA-induced mouse serum. The increased BAFF transcripts was detected in OVA-induced mouse splenocytes. OVA-induced asthma was associated with the increased number of eosinophils in bronchoalveolar lavage fluid (BALF). When TACI:Fc scavenging soluble BAFF was injected to OVA-induced mice, a significant inhibition was detected in the thickness of airway smooth muscle and glycol-containing cellular elements in airway that were visualized by hematoxylin/eosin Y and periodic acid-Schiff staining, respectively. In addition, when mice were treated with TACI:Fc protein, BAFF protein level was decreased in alveolar-associated cells surrounding bronchi of OVA-induced mouse lung tissues compared to control mice. When compared to OVA-induced control, TACI:Fc treatment reduced the percentage of non-lymphoid cells and no changes were detected in lymphoid cell population. Hypodiploid cell formation in BALF was decreased by OVA-challenge but it was recovered by TACI:Fc treatment. Collectively, data suggest that asthmatic symptom could be alleviated by scavenging BAFF and then BAFF could be a novel target for the develpoment of anti-asthmatic agents.
Assuntos
Animais , Feminino , Humanos , Camundongos , Apoptose , Asma/induzido quimicamente , Fator Ativador de Células B/biossíntese , Brônquios/metabolismo , Líquido da Lavagem Broncoalveolar/citologia , Eosinófilos/patologia , Fragmentos Fc das Imunoglobulinas/genética , Imunoglobulina G/genética , Linfócitos/patologia , Camundongos Endogâmicos BALB C , Ovalbumina , Alvéolos Pulmonares/metabolismo , Proteínas Recombinantes de Fusão/genética , Baço/metabolismo , Proteína Transmembrana Ativadora e Interagente do CAML/genéticaRESUMO
B cell activating factor (BAFF) is one of the TNF family member, regulates the survival and maturation of B lymphocyte. BAFF binds to three receptors: BCMA, TACI and BAFF-R. In recent years, studies have revealed important roles of BAFF and its receptors in immune regulation of antibody isotype switching, germinal center maintenance, and T cell co-stimulation, that may provide new drugs in the future for the treatment of autoimmune disorders, lymphoma and B cell immunodeficiencies. Therefore, the structure, expression, receptors, biological function and clinical application of BAFF are briefly summarized in this review.