Non-classical monocyte homing to the gut via α4ß7 integrin mediates macrophage-dependent intestinal wound healing.

OBJECTIVE: To study the role of α4ß7 integrin for gut homing of monocytes and to explore the biological consequences of therapeutic α4ß7 inhibition with regard to intestinal wound healing. DESIGN: We studied the expression of homing markers on monocyte subsets in the peripheral blood and on macrophage subsets in the gut of patients with IBD and controls with flow cytometry and immunohistochemistry. Integrin function was addressed with dynamic adhesion assays and in vivo gut homing assays. In vivo wound healing was studied in mice deficient for or depleted of α4ß7 integrin. RESULTS: Classical and non-classical monocytes were clearly dichotomous regarding homing marker expression including relevant expression of α4ß7 integrin on human and mouse non-classical monocytes but not on classical monocytes. Monocyte-expressed α4ß7 integrin was functionally important for dynamic adhesion to mucosal vascular addressin cell adhesion molecule 1 and in vivo gut homing. Impaired α4ß7-dependent gut homing was associated with reduced (effect size about 20%) and delayed wound healing and suppressed perilesional presence of wound healing macrophages. Non-classical monocytes in the peripheral blood were increased in patients with IBD under clinical treatment with vedolizumab. CONCLUSION: In addition to reported effects on lymphocytes, anti-α4ß7 therapy in IBD also targets non-classical monocytes. Impaired gut homing of such monocytes might lead to a reduction of wound healing macrophages and could potentially explain increased rates of postoperative complications in vedolizumab-treated patients, which have been observed in some studies.

An optical flow-based method to predict infantile cerebral palsy.

Cerebral palsy (CP) is a perinatally acquired nonprogressive brain damage resulting in motor impairment affecting mobility and posture. Early identification of infants with CP is desired to target early interventions and follow-up. During early infancy, distinct motion patterns occur which are highly predictive for later disability. These motor patterns can be observed and recorded. In this paper, a method to predict later CP based on early video recordings of the infants' spontaneous movements, applying optical flow and statistical pattern recognition, is presented. We extract motion information from video recordings of young infants using a total variation related optical flow method. By using wavelet analysis features from motion trajectories of points initiated on a regular grid were extracted and classified using a support vector machine.