Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an anti-inflammatory molecule that negatively regulates the non-canonical nuclear factor-κB pathway. Although TRAF3 haploinsufficiency (TRAF3 HI) can influence innate and adaptive immune cells, its effect on inflammatory bowel disease (IBD) development remains unclear. Here, we report the first case of severe early-onset IBD with a novel TRAF3 variant leading to HI, successfully treated with ustekinumab. A 6-year-old girl with a recurrent parotitis, otitis media, tonsilitis, and atopic dermatitis developed IBD involving the stomach, small intestine, and colon. At diagnosis, the immunoglobulin (Ig)G and IgA levels were relatively high, and lymphocyte subsets showed increased counts of plasmablasts, class-switch recombination B cells, and circulating T-follicular helper cells. Treatment with azathioprine and infliximab failed to maintain remission marked by several relapses accompanied by erythema nodosum and arthritis; however, ustekinumab, an anti-interleukin (IL)-12/23p40 antibody, led to long-term clinical remission, normalizing the Ig level and reducing abnormal lymphocyte counts. Whole-exome sequencing revealed a novel heterozygous mutation in TRAF3 [p.(Pro487Leufs*8)], resulting in TRAF3 under-expression. Our case may highlight the contribution of TRAF3 HI to the development of IBD and provide insights into IBD pathophysiology, suggesting the involvement of the IL-12/23-T-follicular helper cell pathway affected by genetic mutations.

Since the airways are constantly exposed to various pathogens and foreign antigens, various kinds of cells in the airways—including structural cells and immune cells—interact to form a precise defense system against pathogens and antigens that involve both innate immunity and acquired immunity. Accumulating evidence suggests that innate lymphoid cells (ILCs) play critical roles in the maintenance of tissue homeostasis, defense against pathogens and the pathogenesis of inflammatory diseases, especially at body surface mucosal sites such as the airways. ILCs are activated mainly by cytokines, lipid mediators and neuropeptides that are produced by surrounding cells, and they produce large amounts of cytokines that result in inflammation. In addition, ILCs can change their phenotype in response to stimuli from surrounding cells, which enables them to respond promptly to microenvironmental changes. ILCs exhibit substantial heterogeneity, with different phenotypes and functions depending on the organ and type of inflammation, presumably because of differences in microenvironments. Thus, ILCs may be a sensitive detector of microenvironmental changes, and analysis of their phenotype and function at local sites may enable us to better understand the microenvironment in airway diseases. In this review, we aimed to identify molecules that either positively or negatively influence the function and/or plasticity of ILCs and the sources of the molecules in the airways in order to examine the pathophysiology of airway inflammatory diseases and facilitate the issues to be solved.
Adaptive Immunity ; Cellular Microenvironment ; Cytokines ; Homeostasis ; Immunity, Innate ; Inflammation ; Lymphocytes ; Neuropeptides ; Phenotype ; Plastics ; Population Characteristics ; Respiratory Tract Diseases

OBJECTIVES: To clarify the prevalence and characteristics of pain associated with sarcopenia and to verify the usefulness of evaluation of pain for sarcopenia. METHODS: In total, 759 community-dwelling people (aged 65–79 years) with or without sarcopenia and lower limb pain were classified into 4 groups (NSp, nonsarcopenia; NSpP, nonsarcopenia with pain; Sp, sarcopenia; and SpP, sarcopenia with pain). Body composition, motor function, history of fractures since age 50 years, and number of falls in the past 1 year were compared between the groups. RESULTS: Participant proportions by group were: NSp, 53.9%; NSpP, 42.8%; Sp, 1.3%; and SpP, 2.0%. Participants with lower limb pain showed low single leg standing, walking speed, and 2-step value scores and high 25-question Geriatric Locomotive Functional Scale (GLFS-25) score after adjusting for age, sex, body mass index, and presence of sarcopenia. The SpP group showed lower functional reach test and higher GLFS-25 scores than the Sp group. Regarding the history of fractures since 50 years of age and falls in past 1 year, a high retention rate of fracture was noted in the NSpP group. They also experienced significantly more falls in the past 1 year than those in the NSp group. The SpP group noted more falls and fractures although it was insignificant. CONCLUSIONS: The results indicate that participants with lower limb pain showed declining motor function and a high risk for falls and fractures. Sarcopenia could escalate this risk. Therefore, evaluating patients for both pain and sarcopenia may be useful for risk assessment and treatment.
Accidental Falls ; Aged ; Body Composition ; Body Mass Index ; Humans ; Leg ; Lower Extremity ; Prevalence ; Risk Assessment ; Sarcopenia ; Walking