Laboratories : IBS and LCBM - 01/09/2021 – 30/09/2024

Thesis project holders : Véronique ROSSI and Thierry RABILLOUD
Young thesis researcher : Marie LORVELLEC

Abstract: C1s protease initiates the classical complement pathway, previously thought to target only C2 and C4. Recent studies reveal that free active C1s has roles beyond complement activation, including targeting HMGB1. Initially recognized as a nuclear protein, extracellular HMGB1 drives inflammation. This work highlights that fragment f3, generated by C1s cleavage, inhibits pro-inflammatory cytokine secretion. Additionally, its redox state influences HMGB1 digestion and fragment functions. These findings position HMGB1/C1s as key regulators in transitioning from inflammation to resolution phases, offering therapeutic insights.

Publications:
Complement System and Alarmin HMGB1 Crosstalk: For Better or Worse, C. Gaboriaud, M.Lorvellec, V.Rossi, C.Dumestre-Pérard and N.M.Thielens, Frontiers in Immunology, 2022

HMGB1 cleavage by complement C1s and its potent anti-inflammatory product, M.Lorvellec, A.Chouquet, J.Koch, I.Bally, L.Signor, J.Vigne, F.Dalonneau, N.M.Thielens, T.Rabilloud, B.Dalzon, V.Rossi and C.Gaboriaud, Frontiers in Immunology, 2023