bims-actimu 2025-12-14 papers

Issue of 2025–12–14
two papers selected by
Elodie Busch, University of Strasbourg

Immunity. 2025 Dec 09. pii: S1074-7613(25)00511-4. [Epub ahead of print]

The TCR-SUB1-DOCK2 axis promotes autoimmunity by driving pathogenic CD4+ T cell tissue infiltration.

Xiaoxue Li, Wenhua Liang, Weifang Wang, Eilon Sherman, Keling Huang, Feng Wang.

Aberrant tissue infiltration by activated CD4+ T cells is a central driver of autoimmunity, yet the molecular checkpoints governing antigen-specific T cell ingress remain poorly defined. We found that the transcription factor SUB1 was selectively upregulated in CD4+ T cells from individuals with autoimmune diseases. SUB1 expression was induced by the T cell receptor (TCR)-interferon regulatory factor 4 (IRF4) transcription factor axis. Conditional deletion of Sub1 in T cells reduced the expression of migration regulator dedicator of cytokinesis 2 (DOCK2), inhibited Rac-dependent actin polymerization and T cell motility, and prevented the onset of experimental autoimmune encephalomyelitis. Mechanistically, SUB1 underwent liquid-liquid phase separation to form biomolecular condensates that opened chromatin at the Junb and Dock2 loci. It then directly trans-activated Junb transcription and partnered with JUNB to amplify Dock2 transcription. Therefore, SUB1 is a critical gatekeeper of pathogenic T cell trafficking, and by linking TCR signaling to cytoskeletal remodeling, the TCR-SUB1-DOCK2 axis emerges as a tractable, migration-focused therapeutic target in autoimmune disorders.

Keywords: CD4(+) T cells; DOCK2; SUB1; T cell receptor; autoimmune diseases; cell migration; chromatin accessibility; cytoskeletal rearrangement

DOI: https://doi.org/10.1016/j.immuni.2025.11.009

Blood Cell Ther. 2025 Nov 25. 8(4): 281-285

Bone marrow transplantation for leukocyte adhesion deficiency type III: immunosuppressant dosage adjustments against severe T-cell mixed chimerism.

Takashi Koike, Eri Shigematsu, Keisuke Otsubo, Shigeki Ochiai, Yoshifumi Fukuda, Hidefumi Hiramatsu, Hiromasa Yabe.

Allogeneic stem cell transplantation from an HLA-mismatched unrelated donor was performed for a patient with leukocyte adhesion deficiency type III with a myeloablative regimen including full-dose busulfan. Mixed chimerism with donor-derived T cells at less than 10% was observed within 4 weeks after transplantation. Repeated cycles of discontinuation and resumption of tacrolimus early after transplantation were performed with the aim of reversing the recipient-dominant T-cell chimerism. Specifically, tacrolimus was quickly tapered on day 15 and discontinued on day 20 when the recipient's chimerism increased, and resumed upon the observation of early signs of acute graft-versus-host disease, such as fever and skin rash, on day 24. This process was repeated from day 30 to day 44. All subsets, including granulocytes, T cells, and natural killer cells, attained donor chimerism of more than 90% on day 42 after transplantation and 100% at day 82 and beyond. Immunosuppressant dosage adjustments may be a treatment option for mixed chimerism after stem cell transplantation.

Keywords: bone marrow transplantation; immunosuppressant dosage adjustment; leukocyte adhesion deficiency type III; mixed chimerism; unrelated donor

DOI: https://doi.org/10.31547/bct-2025-003