Margiotta, A. | bioRxiv Science

bioRxiv2026

Regulatory T cells modulate bone marrow stromal cell osteogenesis by activating ROCK-myosin axis and cell contractility

Bone regeneration depends not only on the intrinsic signaling in bone marrow-derived mesenchymal stromal cells (BMSC), but also on immune cell-derived cues. Regulatory T cells (Treg) are emerging as immune regulators of tissue repair, yet their direct impact on BMSC osteogenesis remains unexplored. Here, we showed that direct human BMSC-Treg co-culture induced more pronounced osteogenic gene expression and cytokine modulation in BMSC than indirect co-culture. This contact-dependent interaction temporally enhanced BMSC osteogenic gene expression, alkaline phosphatase activity and matrix mineralization by interacting with ROCK-myosin signaling pathway. Exploratory proteomic profiling further revealed enrichment of cytoskeletal, mechanosensitive and osteogenic regulators in BMSC after direct Treg co-culture. Pharmacological inhibition of cell contractility impaired osteogenesis yet Treg co-culture partially restored cytoskeletal integrity and differentiation. These findings identify novel mechanisms behind Treg as direct modulators of BMSC mechanobiology and osteogenesis, highlighting their therapeutic potential in bone regeneration.

cell biology↗

bioRxiv2019

Invariant chain regulates endosomal fusion and maturation through the SNARE Vti1b

Invariant chain (Ii) is an important multifunctional player in the regulation of adaptive immune responses and is responsible for several cellular functions related to MHCI and MHCII antigen loading and antigen presentation. While regulating endosomal trafficking of MHCII and other proteins that bind to Ii, this molecule is able to influence the endosomal pathway delaying the maturation of endosomes to the late endosomal loading compartments. When expressed in cells Ii is found to increase endosomal size, but the mechanisms for this is not known. We used RNAi silencing to identify SNARE proteins controlling Ii induced increase of endosomal size and delay of the endosomal pathway. Ii was found to interact with the SNARE protein Vti1b. Vti1b localized at the contact sites of fusing Ii positive endosomes and a tailless Ii was able to relocate Vti1b to the plasma membrane. Furthermore, silencing Vti1b, abrogated the delay in endosomal maturation induced by Ii expression. In conclusion, Ii interacts with Vti1b and this interaction is fundamental for Ii-mediated alteration of the endosomal pathway. We propose that Ii, by interacting with SNAREs, in particular Vti1B in the biosynthetic pathway of antigen presenting cells, is able to assemble SNARE directed fusion partners in the early part of the endosomal pathway that lead to a slower endosomal maturation for efficient antigen processing and antigen loading.

cell biology↗