In Brief

Immunoregulation

The transcription factor T-bet regulates mucosal T-cell activation in experimental colitis and Crohn's disease.Neurath, M. F. et al. J. Exp. Med. 195, 1129–1143 (2002)

T helper 1 (T_H1) and T_H2 effector cytokines are thought to have pathogenic roles in Crohn's disease and ulcerative colitis, respectively. Here, the authors looked at the role of T-bet — a T-box-family transcription factor that is essential for the development of T_H1 responses — in inflammatory bowel disease. They show that T-bet is highly expressed in the lamina propria T cells of patients with Crohn's disease, but not in the lamina propria T cells of patients with ulcerative colitis. In an induced animal model of colitis, the retroviral transduction of T-bet in CD4⁺ T cells exacerbated disease, whereas T-bet-deficient CD4⁺ T cells failed to induce disease. This identifies T-bet as a putative therapeutic target in Crohn's disease.

B-cell responses

The activation-induced deaminase functions in a postcleavage step of the somatic hypermutation process.Papavasiliou, F. N. & Schatz, D. G. J. Exp. Med. 195, 1193–1198 (2002)

Somatic hypermutation is a process by which the primary B-cell antibody repertoire undergoes antigen-driven diversification, whereas class-switch recombination replaces the constant region of the immunoglobulin heavy chain and, so, alters the effector functions of the antibody. The molecular mechanisms of somatic hypermutation and class-switch recombination are not understood fully, but the recently discovered protein activation-induced cytidine deaminase (AID) has been proposed to have a role in the initiation of both processes by means of the activation of a common nuclease. This paper shows that AID is important for events that occur downstream of the DNA breaks, rather than the process of initiating the breaks.

Myeloid development

Spi-B can functionally replace PU.1 in myeloid but not lymphoid development.Dahl, R. et al. EMBO J. 21, 2220–2230 (2002)

Gene targeting of Pu.1 (Spi1) compared with Spib, two closely related members of the Ets family of transcription factors, resulted in surprisingly different phenotypes. Pu.1^−/− mice lack mature macrophages, neutrophils and lymphoid cells, whereas all haematopoietic lineages develop in Spib^−/− mice. Here, by introducing the Spib complementary DNA into the Pu.1 gene locus by means of homologous recombination, the authors show that Spi-B can replace the function of PU.1 in myeloid development, but not in lymphoid development. The distinct phenotypes of the knockout mice are, therefore, not simply owing to the different expression patterns of these transcription factors — PU.1 has unique functions that cannot be carried out by Spi-B.