About this Research Topic
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that affects the functionality of the joints. It has a high prevalence in the population and supposes a deterioration for the individual and social functions of those affected. It is the consequence of a failure in the self-tolerance mechanisms that culminates in the production of autoantibodies that trigger an inflammatory response affecting the joints.
Two phases can be identified in the development of the disease; the first phase is the induction phase and is mediated by adaptive immunity. The second, effector phase involves the destruction of the joints and is largely coordinated by the innate immune system although the innate immune system is involved in both phases. Cells of the innate immune system, such as monocytes, macrophages or interdigitating cells (IDCs), play a fundamental role in the development, chronicity and eventual resolution of RA in both animal models and humans. These cells, activated by molecular sensors, act in the induction phase as antigen presenting cells and produce cytokines and chemokines that initiate the autoimmune response, triggering an inflammatory response. IDCs present autoantigens to T and B autoreactive cells. However, due to their cellular heterogeneity, some types of IDCs, once activated, produce pro-inflammatory cytokines, while others are tolerogenic and induce the differentiation of Treg cells. Monocytes and macrophages that infiltrate the joints show heterogeneity, polarity and plasticity: M1 macrophages produce pro-inflammatory cytokines and metalloproteinases (MMP) that cause the destruction of bone and cartilage, while M2 macrophages have anti-inflammatory properties and can initiate tissue repair.
Neutrophils also play an important role in the inflammatory response. Recruited to the arthritic synovium, they are activated by immune complexes and certain cytokines. They produce reactive oxygen radicals (ROS) and inflammatory cytokines, inducing a chronic arthritic process. In this scenario, fibroblasts are also transformed and are a source of pro-inflammatory cytokines.
Increasing attention is also being paid to the role played by innate lymphoid cells (ILCs) in inflammatory diseases such as RA. They are distinguished from the rest of the lymphocytes by the absence of specific receptors for antigens. They are most prevalent on body surfaces in contact with the external environment such as skin, intestine or lung, where they are activated by environmental and stress signals. They play an important role in the polarity of the immune response, in protection against pathogens and in tissue homeostasis. The proliferation and abnormal activation of ILC1 and ILC3 may contribute to the development of RA, while the activation of ILC2 may be involved in the remission of the disease.
Given the participation of the innate immune system, knowledge of its participation in inflammatory mechanisms, repair processes and the resolution of the arthritic process is of great importance. This Research Topic aims to provide further knowledge of our current understanding in this field. We therefore welcome the submission of Original Research, Review and Mini-Review articles that cover, but are not limited to, the following topics:
• Sensors and signaling of the innate immune system involved in RA
• Interdigitating cells, innate lymphoid cells and macrophages in the development of RA
• The innate immune system as a target for anti-inflammatory treatment in RA
• The innate immune system as a target for RA remission
• Markers of the innate immune system in the diagnosis and evolution of RA
• Heterogeneity of the innate immune system in driving pathogenesis of RA
• Crosstalk between innate and adaptive immune system in contribution of RA development
Dr. Delgado is the inventor of a patent, licensed to Takeda Pharmaceuticals, exploited in "Alofisel" for the treatment of Crohn's disease-associated complications. The other Topic Editors declare no competing interests with relation to the Research Topic theme.
Two phases can be identified in the development of the disease; the first phase is the induction phase and is mediated by adaptive immunity. The second, effector phase involves the destruction of the joints and is largely coordinated by the innate immune system although the innate immune system is involved in both phases. Cells of the innate immune system, such as monocytes, macrophages or interdigitating cells (IDCs), play a fundamental role in the development, chronicity and eventual resolution of RA in both animal models and humans. These cells, activated by molecular sensors, act in the induction phase as antigen presenting cells and produce cytokines and chemokines that initiate the autoimmune response, triggering an inflammatory response. IDCs present autoantigens to T and B autoreactive cells. However, due to their cellular heterogeneity, some types of IDCs, once activated, produce pro-inflammatory cytokines, while others are tolerogenic and induce the differentiation of Treg cells. Monocytes and macrophages that infiltrate the joints show heterogeneity, polarity and plasticity: M1 macrophages produce pro-inflammatory cytokines and metalloproteinases (MMP) that cause the destruction of bone and cartilage, while M2 macrophages have anti-inflammatory properties and can initiate tissue repair.
Neutrophils also play an important role in the inflammatory response. Recruited to the arthritic synovium, they are activated by immune complexes and certain cytokines. They produce reactive oxygen radicals (ROS) and inflammatory cytokines, inducing a chronic arthritic process. In this scenario, fibroblasts are also transformed and are a source of pro-inflammatory cytokines.
Increasing attention is also being paid to the role played by innate lymphoid cells (ILCs) in inflammatory diseases such as RA. They are distinguished from the rest of the lymphocytes by the absence of specific receptors for antigens. They are most prevalent on body surfaces in contact with the external environment such as skin, intestine or lung, where they are activated by environmental and stress signals. They play an important role in the polarity of the immune response, in protection against pathogens and in tissue homeostasis. The proliferation and abnormal activation of ILC1 and ILC3 may contribute to the development of RA, while the activation of ILC2 may be involved in the remission of the disease.
Given the participation of the innate immune system, knowledge of its participation in inflammatory mechanisms, repair processes and the resolution of the arthritic process is of great importance. This Research Topic aims to provide further knowledge of our current understanding in this field. We therefore welcome the submission of Original Research, Review and Mini-Review articles that cover, but are not limited to, the following topics:
• Sensors and signaling of the innate immune system involved in RA
• Interdigitating cells, innate lymphoid cells and macrophages in the development of RA
• The innate immune system as a target for anti-inflammatory treatment in RA
• The innate immune system as a target for RA remission
• Markers of the innate immune system in the diagnosis and evolution of RA
• Heterogeneity of the innate immune system in driving pathogenesis of RA
• Crosstalk between innate and adaptive immune system in contribution of RA development
Dr. Delgado is the inventor of a patent, licensed to Takeda Pharmaceuticals, exploited in "Alofisel" for the treatment of Crohn's disease-associated complications. The other Topic Editors declare no competing interests with relation to the Research Topic theme.
Keywords: rheumatoid arthritis, inflammation, cytokines, macrophages, monocytes, innate lymphoid cells (ILCs), innate immunity, inflammatory responses, neutrophils, chemokines
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
