ABSTRACT
How the immune system adapts to malnutrition to sustain immunity at barrier surfaces, such as the intestine, remains unclear. Vitamin A deficiency is one of the most common micronutrient deficiencies and is associated with profound defects in adaptive immunity. Here, we found that type 3 innate lymphoid cells (ILC3s) are severely diminished in vitamin A-deficient settings, which results in compromised immunity to acute bacterial infection. However, vitamin A deprivation paradoxically resulted in dramatic expansion of interleukin-13 (IL-13)-producing ILC2s and resistance to nematode infection in mice, which revealed that ILCs are primary sensors of dietary stress. Further, these data indicate that, during malnutrition, a switch to innate type 2 immunity may represent a powerful adaptation of the immune system to promote host survival in the face of ongoing barrier challenges.
Subject(s)
Adaptive Immunity , Immunity, Innate , Lymphocytes/immunology , Micronutrients/deficiency , Vitamin A Deficiency/immunology , Vitamin A/immunology , Animals , Citrobacter rodentium/immunology , Enterobacteriaceae Infections/immunology , Homeodomain Proteins/genetics , Interleukin-13/biosynthesis , Mice , Mice, Inbred C57BL , Mice, Mutant StrainsABSTRACT
The innate and adaptive immune systems in the intestine cooperate to maintain the integrity of the intestinal barrier and to regulate the composition of the resident microbiota. However, little is known about the crosstalk between the innate and adaptive immune systems that contribute to this homeostasis. We find that CD4+ T cells regulate the number and function of barrier-protective innate lymphoid cells (ILCs), as well as production of antimicrobial peptides (AMPs), Reg3γ and Reg3ß. RAG1-/- mice lacking T and B cells had elevated ILC numbers, interleukin-22 (IL-22) production, and AMP expression, which were corrected by replacement of CD4+ T cells. Major histocompatibility class II-/- (MHCII-/-) mice lacking CD4+ T cells also had increased ILCs, IL-22, and AMPs, suggesting that negative regulation by CD4+ T cells occurs at steady state. We utilized transfers and genetically modified mice to show that reduction of IL-22 is mediated by conventional CD4+ T cells and is T-cell receptor dependent. The IL-22-AMP axis responds to commensal bacteria; however, neither the bacterial repertoire nor the gross localization of commensal bacteria differed between MHCII+/- and MHCII-/- littermates. These data define a novel ability of CD4+ T cells to regulate intestinal IL-22-producing ILCs and AMPs.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , Immunity, Innate , Interleukins/metabolism , Intestines/immunology , Lymphocytes/immunology , Adaptive Immunity , Animals , Antimicrobial Cationic Peptides/metabolism , Genes, RAG-1/genetics , Lymphocytes/cytology , Mice , Mice, Knockout , Interleukin-22ABSTRACT
The inflammatory arthritides are a group of chronic, often debilitating disorders characterized by synovial inflammation and progressive joint destruction. The primary diagnostic aim is to recognize the inflammatory arthritis at an early stage, such that therapies may be implemented before irreversible joint destruction has occurred. The radiologist now plays a pivotal role both in making an accurate and early diagnosis of inflammatory arthritis as well as assessing treatment response. This article reviews the current literature and presents our approach to the sonographic assessment of early inflammatory arthritis.
