Volume 15 Issue 7, July 2014

The transcription factors TCF-1 and LEF-1 have diverse roles in differentiation into the CD4⁺ lineage through means both dependent on and independent of the transcription factor Th-POK.

Migrating dendritic cells follow precise navigational chemokine gradients established by lymph node stromal cells through their asymmetric expression of the atypical chemokine receptor CCRL1.

The transcription factors Foxp1 and Foxo1 inhibit the differentiation of follicular helper T cells. On the other hand, the E3 ligase Itch targets Foxo1 for degradation to promote such differentiation.

The pathogenesis of inflammatory bowel disease is orchestrated by specific subsets of cytokine-secreting T cells. The interleukin 9–producing subset of helper T cells contributes to the pathogenesis of inflammatory bowel disease in part by disrupting intestinal barrier function and impairing tissue-repair mechanisms.

Neutrophils are classically known for their role as efficient phagocytes. Nauseef and Borregaard discuss other aspects of their biology, including trafficking, phagosome heterogeneity and the production of ectosomes.

NF-κB activity is regulated by multiple ubiquitin-dependent regulatory steps. Cao and colleagues show that the rhomboid protein Rhbdd3 recognizes K27-linked ubiquitin and prevents IL-6-mediated autoimmunity by recruiting the deubiquitinase A20 to NEMO (IKKγ) kinase complexes.

Antigen-bearing dendritic cells transit through the lymphatics via chemokine receptor CCR7–dependent chemotactic cues. Rot and colleagues show that the atypical chemokine receptor CCRL1 establishes chemokine polarity in the subscapsular sinus that enables entry into the lymph node.

Prior antigenic exposure induces cognate memory responses in B cells. Shlomchik and colleagues show that CD80 and PD-L2 define functionally distinct memory B cells.

Lineage fate in the thymus is imposed by the antagonizing effects of the transcription factors ThPOK and Runx3. Park and colleagues show that ThPOK-induced SOCS factors are required for differentiation into the CD4⁺ T cell lineage.

TCF-1 and LEF-1 are essential for early T cell development. Xue and colleagues show that in DP thymocytes, they control CD4⁺-versus-CD8⁺ T cell lineage 'decisions' and contribute to the establishment of CD8⁺ T cell identity.

The molecular mechanisms that regulate the induction of follicular helper T cells (T_FH cells) remain unclear. Liu and colleagues show that the E3 ubiquitin ligase Itch regulates T_FH cell differentiation through ubiquitination and degradation of the transcription factor Foxo1.

The cell-intrinsic factors that regulate the differentiation of follicular helper T cells remain unclear. Hu and colleagues demonstrate that the transcription factor Foxp1 is critical in inhibiting such differentiation.

The T_H9 subset of helper T cells has specialized roles in parasite immunity. Neurath and colleagues show that T_H9 cells are also important for the pathogenesis of mouse and human colitis by disrupting gut barrier function.

TCR ligation activates the kinase Zap70. Weiss and colleagues, utilizing 'analog-sensitive' Zap70 cells, show that thymocyte positive and negative selection exhibit differential temporal requirements for Zap70 signaling.