IL17F (Interleukin-17F) is a cytokine belonging to the IL-17 family that plays crucial roles in inflammatory responses and autoimmune diseases. IL-17F is closely related to IL-17A (the prototypical IL-17 cytokine) and has been increasingly studied for its involvement in neuroinflammation and neurodegenerative diseases[@kuestner2007].
<div class="infobox infobox-gene">
| Property | Value | |----------|-------| | Gene Symbol | IL17F | | Full Name | Interleukin-17F | | Chromosomal Location | 6p12.1 | | NCBI Gene ID | 112744 | | OMIM ID | 607351 | | Ensembl ID | ENSG00000139324 | | UniProt ID | Q8WWI1 | | Encoded Protein | Interleukin-17F | | Protein Family | IL-17 family | | Molecular Weight | ~34 kDa (219 amino acids) |
IL17F is located in a cluster with other IL-17 family genes:
IL17A: Adjacent gene (~25 kb upstream)
IL17F: Can form heterodimers with IL-17A
Protein Function
Structure
IL-17F is a homodimeric cytokine[@gaffen2011]:
Monomer: ~35 kDa
Active form: Disulfide-linked homodimer (IL-17F) or heterodimer (IL-17A/F)
Structure: Cysteine knot fold unique to IL-17 family
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IL17F Gene
Overview
IL17F (Interleukin-17F) is a cytokine belonging to the IL-17 family that plays crucial roles in inflammatory responses and autoimmune diseases. IL-17F is closely related to IL-17A (the prototypical IL-17 cytokine) and has been increasingly studied for its involvement in neuroinflammation and neurodegenerative diseases[@kuestner2007].
<div class="infobox infobox-gene">
| Property | Value | |----------|-------| | Gene Symbol | IL17F | | Full Name | Interleukin-17F | | Chromosomal Location | 6p12.1 | | NCBI Gene ID | 112744 | | OMIM ID | 607351 | | Ensembl ID | ENSG00000139324 | | UniProt ID | Q8WWI1 | | Encoded Protein | Interleukin-17F | | Protein Family | IL-17 family | | Molecular Weight | ~34 kDa (219 amino acids) |
Glial Activation: Promotes astrocyte and microglial inflammatory responses
Cytokine Induction: Stimulates production of IL-6, TNF-alpha, IL-1beta in CNS
Chemokine Production: Attracts immune cells to the brain
Synaptic Dysfunction: May contribute to synaptic loss
Disease Associations
Alzheimer's Disease
IL-17F has been implicated in AD pathogenesis[@sutinen2012]:
Elevated IL-17F in AD patient serum and CSF
Promotes neuroinflammation and amyloid pathology
May interact with other IL-17 family cytokines
Parkinson's Disease
Evidence for IL-17F involvement in PD[@reynolds2010]:
Increased IL-17F in PD patient samples
Associated with disease severity
Contributes to dopaminergic neuron vulnerability
Th17/IL-17F axis in PD pathophysiology
Multiple Sclerosis
IL-17F is strongly associated with MS[@lock2002]:
MS patients: Elevated serum and CSF IL-17F levels
Th17 cells: Key pathogenic cells in MS
Animal models: IL-17F contributes to EAE severity
Therapeutic targeting: IL-17F antibodies in development
Amyotrophic Lateral Sclerosis
Elevated IL-17F in ALS patient samples
Associated with disease progression
May contribute to motor neuron inflammation
Other Conditions
Autoimmune diseases: Asthma, psoriasis, IBD
Rheumatoid arthritis: Synovial inflammation
Psoriasis: Primary disease association
Therapeutic Targeting
Strategies
| Approach | Mechanism | Status | |----------|-----------|--------| | Secukinumab | Anti-IL-17A antibody | Approved for psoriasis, psoriatic arthritis | | Ixekizumab | Anti-IL-17A antibody | Approved | | Brodalumab | IL-17RA blocker | Approved | | Anti-IL-17F antibodies | Neutralizing IL-17F | In development | | JAK inhibitors | Block downstream signaling | Approved for some conditions |
Challenges for Neurodegeneration
Blood-brain barrier penetration
Targeting CNS vs. peripheral immune system
Balancing beneficial vs. pathogenic inflammation
Key Publications
[Kuestner RE, et al. (2007). The IL-17 family of cytokines and receptors. J Exp Med 204(2):161-170](https://pubmed.ncbi.nlm.nih.gov/17200410/)
[Gaffen SL. (2011). IL-17 signaling in immunity and inflammation. Nat Rev Immunol 11(9):505-517](https://doi.org/10.1038/nri2990)
[Kolls JK, Lindén A. (2004). Interleukin-17 family members and inflammation. Immunity 21(4):467-476](https://pubmed.ncbi.nlm.nih.gov/15482125/)
[Waisman A, et al. (2015). The IL-17 family of cytokines in the central nervous system. J Exp Med 212(2):135-142](https://doi.org/10.1084/jem.20141764)
[Moynes DM, et al. (2014). IL-17 in the CNS: implications for the pathogenesis of neurodegenerative disorders. J Neuroinflammation 11:189](https://doi.org/10.1186/s12974-014-0189-0)
[Sutinen EM, et al. (2012). Inflammatory biomarkers in Alzheimer's disease. J Alzheimers Dis 31(3):659-668](https://pubmed.ncbi.nlm.nih.gov/22555375/)
[Kuestner RE, et al., The IL-17 family of cytokines and receptors. J Exp Med 2007 (2007)](https://pubmed.ncbi.nlm.nih.gov/17200410/)
[Unknown, Gaffen SL. IL-17 signaling in immunity and inflammation. Nat Rev Immunol 2011 (2011)](https://doi.org/10.1038/nri2990)
[Unknown, Kolls JK, Lindén A. Interleukin-17 family members and inflammation. Immunity 2004 (2004)](https://pubmed.ncbi.nlm.nih.gov/15482125/)
[Waisman A, et al., The IL-17 family of cytokines in the central nervous system. J Exp Med 2015 (2015)](https://doi.org/10.1084/jem.20141764)
[Moynes DM, et al., IL-17 in the CNS: implications for neurodegenerative disorders. J Neuroinflammation 2014 (2014)](https://doi.org/10.1186/s12974-014-0189-0)
[Sutinen EM, et al., Inflammatory biomarkers in Alzheimer's disease. J Alzheimers Dis 2012 (2012)](https://pubmed.ncbi.nlm.nih.gov/22555375/)