Regulation of immunity at tissue sites of inflammation

Abstract

The acquisition and execution of CD4 effector function are tightly regulated and spatially compartmentalized. In the lymph node (LN), naïve CD4+ T cells acquire specialized functions by means of expression of distinct cytokines and acquire distinct homing properties. Therefore, both the function and subsequent localization of effector cells appears to be predetermined during differentiation in the LN. Our studies with the protozoa Leishmania major suggest that this centrally (LN) generated effector repertoire can be further edited at the infected tissue site. Cytokine production in the inflamed tissue can be modulated at a number of levels including chemokine-driven differential recruitment of effector cells, the provision of signals for effector cell function and suppression by regulatory T cells (Tregs). The concept that tissue resident pathogens may subvert the centrally generated cytokine repertoire has important therapeutic implications. Novel therapies that focus on manipulating the local infection site to encourage appropriate recruitment or activation of effectors may be particularly beneficial.

Enterobacter sakazakii Targets DC-SIGN to Induce Immunosuppressive Responses in Dendritic Cells by Modulating MAPKs

“…2A–C). The interference with DC maturation by ES raised the question, whether the bacteria would inhibit maturation induced by the LPS or maturation cocktail of TNF-α, IL-1β, and PGE-2, which are shown to be present at the site of infection in several other studies (52). Despite pretreatment with these inducers, DCs subsequently infected with OmpA+ ES showed down-regulation of maturation markers CD40, CD86, and HLA-DR (Fig.…”

Surge in regulatory cells does not prevent onset of hyperglycemia in NOD mice

“…Reciprocally, although there is convincing evidence that Treg are functionally sufficient in aged NOD mice [3,12,25,29,30], their viability and activity are regulated by numerous environmental factors such as modulation of cytokines by cytotoxic cells and the injured islets themselves [50,[52][53][54]. Even if suppressive activity is thoroughly assessed in vitro, it often does not reflect the activities within the inflammatory infiltrates [46,47,50], their state of activation varies [55] and adjusts continuously to the environment [56]. Beyond the complexity of the mechanisms of Treg-mediated suppression [57,58], diversity of inbred NOD colonies, age and gender are likely to yield very different outcomes in response to various experimental procedures [59].…”

Immunology at the University of Rochester

“…Several investigators in the Autoimmunity Center of Excellence are studying this disease in both humans and a variety of animal models [1, 2]. Cancer has long been the focus of many different research programs, which are represented in this issue by studies on tumor metastases [3] and the role of heat shock proteins in eliciting anti-tumor immunity [4], but several other investigators are exploring many different aspects of this important disease with the goal of finding better therapies.…”

“…Virtually all of the different kinds of cells of the immune system are being studied including B lymphocytes [1], T lymphocytes [2, 4, 7–12], antigen presenting cells [12], and platelets [13]. Many different receptors on these cells and how they affect cellular functions are being explored.…”

“…Examples include the integrin molecules expressed by a wide range of leucocytes [8] and CD28 on T cells, and its mechanisms of stimulation [9]. Trafficking of immune cells is of particular interest to a number of investigators both in terms of mechanisms [7, 8] and how they function at tissue sites of inflammation [2] or tumor growth [3]. …”