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Table 1 Types of IL-17-producing cells [8, 12, 33, 36, 38, 76–80]

From: Mechanistic rationales for targeting interleukin-17A in spondyloarthritis

Cell type

Description

Adaptive Th17 cells

• A subset of activated CD4+ T helper cells that produce high levels of IL-17A, IL-17F, and IL-22, and express IL-23R • CD4+ TCRα/β+ Th17 cells are a well characterized source of IL-17 that play a key role in immune inflammatory responses

Natural Th17 cells

• Subset of thymic Th17 cells that acquire effector function prior to peripheral antigen exposure • These cells have different TCR gene usage and signaling properties compared with conventional Th17 cells

γ/δ T cells

• Potent source of innate IL-17 produced independently of IL-6 • Properties are similar to Th17 cells (e.g., expression of CCR6, IL-23R, and RORγt); these cells also express TLR1, TLR2, and Dectin-1 • Levels of IL-17-producing γ/δ T cells increase during some types of bacterial infections • Different subsets of γ/δ T cells in the thymus produce either IL-17 or IFNγ • Major source of gut-protective IL-17, which acts independently from IL-23

iNKT cells

• Cells that express a restricted TCR that recognizes glycolipid antigens • May provide an alternative source of IL-17 when IL-6 is not present to stimulate Th17 cells • IL-17+ cells express IL-23R and IL-1R1

Tc17 cells

• Subset of CD8+ cells that produces IL-17 • May play a role in pathogenic skin and joint inflammation in psoriasis and PsA, respectively

ILC3s

• Subset of ILCs defined by their capacity to produce IL-17A and/or IL-22 • The role of ILCs in SpA and other forms of destructive arthritis is unclear because cell numbers are generally low

Neutrophils

• Source of IL-17 in effector phase of arthritis • Myeloperoxidase+ and CD15+ neutrophils have been identified as sources of IL-17 in facet joints of patients with SpA

Mast cells

• Primary source of IL-17+ cells in synovial fluid of patients with SpA as a result of innate immune responses

  1. CCR6 C-C chemokine receptor type 6, IFN interferon, IL interleukin, ILC innate lymphoid cell, iNKT cells invariant natural killer T cells, PsA psoriatic arthritis, ROR retinoic orphan receptor, SpA spondyloarthritis, TCR T-cell receptor, Th T-helper, TLR Toll-like receptor