No abstract

Fibroblastic reticular cells (FRCs) are immunologically specialized myofibroblasts of lymphoid organ, and FRC maturation is essential for structural and functional properties of lymph nodes (LNs). Here we show that YAP and TAZ (YAP/TAZ), the final effectors of Hippo signaling, regulate FRC commitment and maturation. Selective depletion of YAP/TAZ in FRCs impairs FRC growth and differentiation and compromises the structural organization of LNs, whereas hyperactivation of YAP/TAZ enhances myofibroblastic characteristics of FRCs and aggravates LN fibrosis. Mechanistically, the interaction between YAP/TAZ and p52 promotes chemokine expression that is required for commitment of FRC lineage prior to lymphotoxin-β receptor (LTβR) engagement, whereas LTβR activation suppresses YAP/TAZ activity for FRC maturation. Our findings thus present YAP/TAZ as critical regulators of commitment and maturation of FRCs, and hold promise for better understanding of FRC-mediated pathophysiologic processes.

Study design: Pott's paraplegic patients with severe spinal deformity were reviewed retrospectively after being treated with chemotherapy and/or decompressive surgery. Objectives: To determine the most appropriate treatment protocol and to predict the prognosis for Pott's paraplegics with severe spinal deformity. Setting:

We retrospectively reviewed 15 children (four with paralysis) and 39 adults (10 with paralysis) with tuberculosis of the cervical spine to assess the drug responses, disease arrest, and healing times. Ten children and 13 adults were treated nonoperatively, while anterior débridement was performed in five children (two with paralysis) and anterior radical surgery in 26 adults (10 with paralysis). Triple chemotherapy (isoniazid, rifampin, ethambutol [or pyrazinamide for children]) was given to all patients for 12 months. The tuberculosis began to arrest after 3 months of chemotherapy and healed within 12 months. Spontaneous fusion occurred in all adults but only two of the 10 children. Surgical fusion was achieved within 12 to 16 weeks in adults. In nonoperated patients, an initial kyphosis of 12 degrees progressed to 17 degrees at final followup in the children and an initial kyphosis of 9 degrees progressed to 13 degrees in 13 adults. In operated patients, the initial kyphosis of 13 degrees in adults became 2 degrees at the time of the fusion, while the initial kyphosis of 14 degrees in the five children progressed to 18 degrees. Patients with paraplegia recovered completely within 14 days on average (range, 1-42 days) after treatment. Recovery was gradual in the nonoperative group, while it occurred within 3 days in the operative group.