IL-17A, produced primarily by Th17 cells, plays a critical role in the pathogenesis of which of the following diseases, and acts mainly by stimulating what cellular response?
- A Ankylosing spondylitis — stimulates epithelial and stromal cells to produce CXC chemokines (IL-8) and G-CSF, recruiting neutrophils to sites of entheseal inflammation ✓
- B Type 1 diabetes — activates pancreatic beta cells to undergo Fas-FasL apoptosis
- C Crohn's disease — stimulates intestinal epithelial M cells to present luminal antigens to dendritic cells
- D Multiple sclerosis — directly disrupts tight junctions in the blood-brain barrier by activating MMP-9 in astrocytes
Explanation
IL-17A (and its closely related IL-17F) are the signature cytokines of Th17 cells and are centrally implicated in spondyloarthropathies including ankylosing spondylitis (AS), psoriatic arthritis, and inflammatory bowel disease-related arthropathy. At entheses (tendon/ligament insertions), IL-17A acts on local fibroblasts, osteoblasts, and epithelial cells to upregulate CXC chemokines (CXCL1/5/8/IL-8), G-CSF and M-CSF, creating a neutrophil and monocyte-rich inflammatory milieu. This drives periostitis and new bone formation characteristic of AS. Secukinumab and ixekizumab (IL-17A inhibitors) are approved for AS, demonstrating this pathway's therapeutic relevance. IL-17A is not the primary mechanism in T1DM beta cell death, M cell antigen presentation in Crohn's, or BBB disruption in MS.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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