Selective inhibition of IL-6 trans-signalling reveals distinct mechanisms of human classic and trans-signalling receptor-complex formation.

A human-specific antibody selectively inhibits interleukin-6 trans-signalling while preserving classic signalling, revealing distinct receptor assembly mechanisms.

• Why it matters: Current therapies block both pathways of interleukin-6, disrupting essential functions; selective inhibition could improve treatment specificity and reduce side effects.
• What they did: The researchers developed a high-affinity antibody targeting domain D2 of human interleukin-6 receptor, blocking trans-signalling without affecting ligand binding or classic signalling.
• The result: This selective blockade demonstrates that interleukin-6 classic and trans-signalling involve distinct receptor complexes, enabling targeted modulation of inflammatory responses while maintaining regenerative functions.