▶️ What is the difference between activating and inhibitory Fc receptors?

– The difference between activating and inhibitory Fc receptors is that activating Fc receptors trigger pro-inflammatory pathways and enhance the immune response, while inhibitory Fc receptors dampen the immune response and prevent excessive inflammation.

– Fc receptors are proteins that bind to the Fc region of antibodies and modulate the function of immune cells. There are different types of Fc receptors, such as FcγR, FcεR, FcαR, and FcμR, that recognize different classes of antibodies, such as IgG, IgE, IgA, and IgM.

– Activating Fc receptors have an immunoreceptor tyrosine-based activation motif (ITAM) in their cytoplasmic tail or associate with ITAM-containing adaptor molecules, such as CD3ζ or FcRγ.

– When activating Fc receptors bind to antibodies that are attached to antigens or immune complexes, they recruit and activate tyrosine kinases, such as Src and Syk, that initiate a cascade of signaling events that lead to the activation and degranulation of the immune cell. Activating Fc receptors can stimulate: phagocytosis, cytotoxicity, antibody production, cytokine release, and inflammation.

– Fc receptors have an immunoreceptor tyrosine-based inhibition motif (ITIM) in their cytoplasmic tail. When inhibitory Fc receptors bind to antibodies that are attached to antigens or immune complexes, they recruit and activate tyrosine phosphatases, such as SHP-1 and SHP-2, that inhibit the signaling events triggered by activating Fc receptors or antigen receptors. Inhibitory Fc receptors can suppress phagocytosis, cytotoxicity, antibody production, cytokine release, and inflammation.

– The balance between activating and inhibitory Fc receptors determines the outcome and magnitude of the immune response. A dysregulation of this balance can lead to autoimmune diseases, allergic reactions, or impaired immunity.

▶️ What is the role of Fc receptors in autoimmune diseases?

– The role of Fc receptors in autoimmune diseases is to mediate the interaction between autoantibodies and self-antigens, which can lead to inflammation, tissue damage, and disease symptoms. Fc receptors are proteins that bind to the Fc region of antibodies and modulate the function of immune cells. There are different types of Fc receptors, such as FcγR, FcεR, FcαR, and FcμR, that recognize different classes of antibodies, such as IgG, IgE, IgA, and IgM.

– Fc receptors can be classified into activating and inhibitory types, depending on their signaling motifs and functions. Activating Fc receptors have an immunoreceptor tyrosine-based activation motif (ITAM) or associate with ITAM-containing adaptor molecules, such as CD3ζ or FcRγ. When activating Fc receptors bind to antibodies that are attached to antigens or immune complexes, they trigger pro-inflammatory pathways and enhance the immune response. Inhibitory Fc receptors have an immunoreceptor tyrosine-based inhibition motif (ITIM) in their cytoplasmic tail. When inhibitory Fc receptors bind to antibodies that are attached to antigens or immune complexes, they dampen the immune response and prevent excessive inflammation.

– In autoimmune diseases, the balance between activating and inhibitory Fc receptors is disturbed, resulting in a dysregulated immune response against self-antigens. For example, in rheumatoid arthritis, a chronic inflammatory disease of the joints, autoantibodies to citrullinated proteins form immune complexes that activate FcγRs on macrophages and neutrophils, leading to the release of pro-inflammatory cytokines and reactive oxygen species that cause joint damage. In contrast, inhibitory FcγRIIB can suppress the activation of B cells and plasma cells that produce autoantibodies, as well as the activation of mast cells and basophils that release histamine and other mediators of inflammation.

– The role of Fc receptors in autoimmune diseases can also depend on their genetic variants, expression levels, ligand affinity, and cellular distribution. For example, polymorphisms in the genes encoding FcγRs can affect their binding ability to different subclasses of IgG and influence their susceptibility or resistance to autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, or immune thrombocytopenia. The expression levels of FcγRs can also vary depending on the cell type, activation state, cytokine environment, or disease stage. The ligand affinity of FcγRs can be modulated by factors such as antibody glycosylation, antigen density, or antibody isotype switching. The cellular distribution of FcγRs can also determine their accessibility and availability for antibody binding.

– The role of Fc receptors in autoimmune diseases has important implications for diagnosis and therapy. For example, measuring the levels of autoantibodies and their subclasses can help identify the type and severity of autoimmune diseases. Targeting the interaction between autoantibodies and Fc receptors can help modulate the immune response and reduce inflammation and tissue damage. For example, blocking activating Fc receptors with monoclonal antibodies or small molecules can inhibit the formation or clearance of immune complexes and prevent their pro-inflammatory effects. Enhancing inhibitory Fc receptors with agonists or fusion proteins can suppress the production or function of autoantibodies and restore immune tolerance.

– I hope this information helps you understand more about the difference between activating and inhibitory Fc receptors. If you have any questions and for further clarification please feel free to ask me.