Tissue stroma as a regulator of leukocyte recruitment in inflammation.

The stromal milieu (cellular and matrix components) helps establish tissue "address-codes" that direct leukocyte behavior in inflamed tissue. Coordinated interactions among the stroma, leukocytes, and ECs dictate which leukocytes are recruited, whether they are retained within the inflamed site, and how long they survive. Herein, we discuss how the stromal milieu influences the leukocyte recruitment cascade. Moreover, we explore how corruption of the stromal phenotype in chronic inflammatory diseases contributes to undesired, continuous recruitment of leukocytes. Emerging complex, multicellular, multilayered (co-)culture models are now addressing the molecular circuitry involved in regulating stromal organization during inflammation. Understanding context-specific changes in pro- or anti-inflammatory agents derived from the stroma, such as IL-6 (and its cofactors), is important for the generation of therapeutic strategies that restore the balance between recruitment and clearance of the inflammatory infiltrate in chronic disease.