Developmental immunology

Abnormal bone marrow stroma in mice deficient for nemo-like kinase, Nlk. Kortenjann, M. et al. Eur. J. Immunol. 31, 3580–3587 (2001) [PubMed]

Kortenjann et al. investigated the in vivo role of Nemo-like kinase (Nlk), a serine/threonine kinase that connects MAP kinase and Wnt signalling pathways, by generating Nlk−/− mice. The complex phenotype of these mice depended on their genetic background. 129/Sv Nlk−/− mice, among other defects, developed abnormal bone marrow stroma, resulting in increased numbers of adipocytes, large blood sinuses and an absence of bone-lining cells. These mice represent a new model in which the genetic requirements of bone marrow stromal differentiation can be studied.

Autoimmunity

Systemic sclerosis (scleroderma): specific autoantigen genes are selectively overexpressed in scleroderma fibroblasts. Zhou, X. et al. J. Immunol. 167, 7126–7133 (2001) [PubMed]

Autoimmune mechanisms have been implicated in the pathogenesis of systemic sclerosis (SSc), a multisystem disorder of connective tissue. Here, cDNA microarrays were used to analyse the gene-expression profiles of SSc dermal fibroblasts. In comparison to normal control fibroblasts, SSc fibroblasts from either affected or unaffected skin selectively overexpressed specific autoantigen genes.

T-cell development

Friend of GATA-1 represses GATA-3-dependent activity in CD4+ T cells. Zhou, M. et al. J. Exp. Med. 194, 1461–1471 (2001) [PubMed]

The friend of GATA (FOG)-1 protein is known to regulate activity of GATA transcription factors at several stages of haematopoietic development, but whether it regulates GATA-3 activity in developing T cells was unknown. Here, Zhou et al. show that FOG-1 represses GATA-3-dependent activation of the IL5 promoter in T cells, and that overexpression of FOG-1 during primary activation of naive T cells inhibits TH2 development in CD4+ T cells.

Antigen presentation

Multiple defects in antigen presentation and T-cell development by mice expressing cytoplasmic tail-truncated CD1d. Chiu, Y-H. et al. Nature Immunol. 3, 55–60 (2002) [PubMed]

CD1 molecules are non-polymorphic, MHC class I-like molecules that present lipid antigens to T cells. To investigate the trafficking and presentation pathway for CD1d, Chiu et al. generated knock-in mice expressing CD1d with a truncated cytoplasmic tail. The results show that the tyrosine motif in the cytoplasmic tail is important for intracellular trafficking of CD1 and the development of subsets of CD1d-restricted T cells.