Roles of Fc Receptors in Disease and Therapy

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Background

Fc receptors (FcR) interact with the constant domains of antibodies. The family of FcR consists of at least 5 subtypes, defined by the isotypes they engage and by the role they play: FcγR and FcRn bind IgG, FcεRI bind IgE; FcμR bind IgM and FcαRI bind IgA. In addition, there are a number of non-classical FcR, including those that interact with IgGs within the cell, such as TRIM-21, as well as receptors that engage multiple isotypes such as the polymeric Ig receptor (PIGR). FcRn plays a major role in the regulation of the half-life of IgG and albumin as well as placental transport. Therefore, FcR are major players in autoimmunity, mucosal immunity and tumor immune surveillance. FcεRI is best known for mediating allergic reactions whereas FcγR offer immune defense by means of various effector functions against viral infections, cancer and immune-mediated diseases. In recent years, different FcγR have been shown to be involved in neurodegenerative disorders including Parkinson’s disease and Multiple Sclerosis. These diverse roles in various diseases underscore the potential of targeting FcR for therapeutic purposes.

Recently, FcR have been harnessed as therapeutic targets through antibody engineering. The Fc portions of antibodies have been manipulated to enhance or minimize the interactions with specific FcR to deliver increased immunotherapy for cancer, autoimmunity and virus infections. These FcR interactions are also of key importance in developing antibody-drug conjugates, including immunotoxins and immunocytokines, as well as multivalent and bispecific antibodies. Clearly, a thorough characterization of how various FcR function and are regulated during disease progression is needed in order to understand and improve antibody-based immunotherapy.

This Research Topic will focus on (i) the diverse immunological functions of the different FcR; (ii) how interventions targeting FcR may improve treatment and (iii) the challenges in targeting FcR. We welcome the submission of Review, Mini-Review, Original Research, Classification, Perspective, Opinion, Technology Reports, Method, Clinical Trial and Hypothesis and Theory articles within, but not limited to, the following sub-topics:

1. The role of FcR in disease.
2. The importance of FcR in immunotherapy.
3. Antibody engineering to harness FcR .
4. Cell or organ-specific FcR.
5. The role of non-classical FcR in immunity and disease.

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.

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