Issues

Rubinsztein, Bento, and Deretic discuss the beneficial roles of autophagy in the context of infectious and neurodegenerative diseases.

Aspelund et al. discover the presence of a lymphatic vessel network in the dura mater of the mouse brain and show that these dural lymphatic vessels are important for the clearance of macromolecules from the brain.

The transcription factor c-Myb plays a role in establishing long-lived plasma cell populations in the bone marrow by affecting migration responses to chemokine gradients. The absence of c-Myb results in an absence of IgG⁺ antigen-specific plasma cells in the bone marrow following immunization or virus infection.

Barnes et al. show that a bioactive lipid, lysophosphatidylserine, negatively influences T reg cell accumulation and activity through one of its receptors, GPR174. The authors speculate that GPR174 antagonism may be therapeutic for autoimmune diseases.

CD99 is a critical regulator of leukocyte transendothelial migration (TEM). Watson et al. describe the CD99 signaling pathway responsible. This involves a complex of CD99 with the A-kinase anchoring protein ezrin and soluble adenylyl cyclase that activates protein kinase A during leukocyte TEM.

Kitamura et al. find a role for metastasis-associated macrophage (MAM) chemokine pathways CCL2–CCR2 and CCL3–CCR1 in promoting breast cancer cell pulmonary metastasis. Genetic deletion of CCR1 or CCL3 in a mouse model of breast cancer cell metastasis prevents MAM retention in the lung, reduces MAM-cancer cell interactions and reduces the number of lung metastatic foci.

In human melanoma biopsies and a murine cutaneous wound model, Lee et al. identify the Dishevelled-binding protein CXXC5 as a negative modulator of skin wound healing. CXXC5-deficient mice present accelerated wound healing as well as keratin and collagen synthesis. CXXC5, interacting with Dvl, operates as a negative feedback regulator of Wnt/β-catenin signaling and may represent a potential target for wound treatment.

Holmes et al. demonstrate that the protein tyrosine phosphatase PEP (PTPN22 in humans) associated with lupus and other autoimmune diseases, inhibits IFN-α receptor signaling in mice. PEP-deficient hematopoietic progenitors demonstrate increased IFNAR signaling, IFN-inducible gene expression and proliferation. PEP-deficient mice treated with IFN-α exhibit lupus-like disease and profound defects in hematopoiesis, resulting in cytopenia.

Rahimpour et al. use MR1 tetramers to characterize the heterogeneous population of mouse MAIT cells and find a close resemblance to their human counterparts. These findings will provide the foundation for further investigation of MAIT cells in health and disease.

Ungerbäck et al. show that transcription factors Ebf1 and Pax5 act in a coordinated, dose-dependent manner to preserve B-lineage cell fate. Combined heterozygous loss of both transcription factors results in increased T cell lineage skewing in B cell progenitors.

Using PD-1–deficient mice and co-adoptive transfer approaches, Odorizzi et al. demonstrate that PD-1 is not required for the induction of CD8⁺ T cell exhaustion (T_EX) in chronic LCMV infection. The absence of PD-1 leads to more cytotoxic, but terminally differentiated T_EX, with compromised long-term durability. PD-1 may well serve to protect T_EX from excessive overstimulation, proliferation, and terminal differentiation.