Journal of Experimental Medicine Commentaries

Masking MALT1: the paracaspase's potential for cancer therapy

Vucic, D., Dixit, V. M. — Mon, 26 Oct 2009 09:19:00 PDT

A key feature of aggressive B cell lymphomas is constitutive NF-B activation, which requires signals from the CARD11–BCL-10–MALT1 (CMB) complex. The unique enzymatic activity of MALT1 degrades one of its binding partners, BCL-10, as well as the NF-B inhibitor A20. New data shows that targeting MALT1 protease activity may be a promising therapeutic strategy for treating aggressive B cell lymphomas.

Revisiting Crohn's disease as a primary immunodeficiency of macrophages

Casanova, J.-L., Abel, L. — Mon, 31 Aug 2009 10:07:13 PDT

Despite two decades of mouse immunology and human genetics studies, the pathogenesis of Crohn's disease (CD) remains elusive. New clinical investigations suggest that CD may be caused by inborn errors of macrophages. These errors may result in impaired attraction of granulocytes to the gut wall, causing impaired clearance of intruding bacteria, thereby precipitating the formation of granulomas. This theory paves the way for a macrophage-based Mendelian genetic dissection of CD.

Nine lives: plasticity among T helper cell subsets

Locksley, R. M. — Mon, 03 Aug 2009 10:02:14 PDT

The division of labor among two types of T helper (Th) subsets, first described over 20 yr ago, has been buffeted by the discovery of new subsets and new cytokines that can be coaxed out of T cells with increasing disregard for the subset of origin. Although Th17 cells and regulatory T (T reg) cells are widely accepted subsets, and others are being proposed, their plasticity is difficult to reconcile with the definitions of Th subsets as put forth in the initial description of Th1 and Th2 cells. A deeper molecular context will be required to reconcile the ever-increasing complexity of effector T cells.

Vicious circle: systemic autoreactivity in Ro52/TRIM21-deficient mice

Bolland, S., Garcia-Sastre, A. — Mon, 03 Aug 2009 10:02:14 PDT

Dysregulated innate responses, particularly excessive activation of interferon (IFN) pathways, have been implicated in the development of autoimmune pathologies. Autoreactivity frequently targets IFN-inducible genes such as the Ro autoantigens, which ubiquitinate and inhibit interferon regulatory factors (IRFs). A new study validates the role of these common autoantigens in preventing autoimmunity. The findings reveal that injury-induced systemic autoimmune disease is exacerbated in the absence of Ro52/Trim21 and is driven by the IL-23–Th17 pathway.