Reciprocal Desensitization of CCR5 and CD4 Is Mediated by IL-16 and Macrophage-Inflammatory Protein-1β, Respectively

Mashikian, Margaret Vallen; Ryan, Thomas C.; Seman, Ann; Brazer, William; Center, David M.; Cruikshank, William W.

doi:10.4049/jimmunol.163.6.3123

Cited by 43 publications

(2 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 31 MIP1b‐mediated recruitment and activation of immune cells are essential for the initiation and maintenance of immune responses, as well as the resolution of inflammation. 32 The precise mechanisms underlying the involvement of MIP1b in the pathogenesis of muscular dystrophy remain largely elusive, and there is limited literature available on this topic. One possible mechanism by which MIP1b may contribute to sarcopenia is through the recruitment and activation of immune cells, such as macrophages and T cells, in affected muscle tissues.…”

Section: Discussionmentioning

confidence: 99%

“…MIP1b exerts its effects by binding to CCR5 and CCR1 31 . MIP1b‐mediated recruitment and activation of immune cells are essential for the initiation and maintenance of immune responses, as well as the resolution of inflammation 32 . The precise mechanisms underlying the involvement of MIP1b in the pathogenesis of muscular dystrophy remain largely elusive, and there is limited literature available on this topic.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mapping the causal associations of cytokines with sarcopenia and aging traits: Evidence from bidirectional Mendelian randomization

Liu,

Fu,

et al. 2024

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

BackgroundCytokines and growth factors may serve as a bridge in studying the causal relationships between inflammaging and sarcopenia due to their roles in inflammaging. In this study, we aim to explore the causal association of cytokines with sarcopenia and aging traits and further identify the significant inflammation factors.MethodsBidirectional Mendelian randomization (MR) analysis was used to identify the causality. Forty‐one kinds of circulation cytokines and growth factors were set as exposures, and the data were from a summary genome‐wide association study (GWAS) containing three cohorts with 8293 healthy participants of European ancestry from 1983 to 2011. Hand grip strength, adjusted appendicular lean mass (AALM), usual walking pace, moderate‐to‐vigorous physical activity (MVPA) levels, able to walk or cycle unaided for 10 min (AWCU10) and telomere length were selected as outcomes. Data for outcomes were obtained from meta‐GWAS and the UK Biobank, and sample sizes ranged from 69 537 to 472 174. Low hand grip strength was defined by the European Working Group on Sarcopenia in Older People (EWGSOP) and Foundation for the National Institutes of Health (FNIH) cut‐off points, respectively. Other outcome traits were defined and measured according to the UK Biobank and raw cohorts' criteria. We set two significance thresholds for single nucleotide polymorphisms (SNPs) associated with exposures to obtain adequate SNPs (5 × 10−6 and 5 × 10−8). Inverse‐variance weighted, MR‐Egger and weighted median were employed to estimate the causality.ResultsTwenty‐seven factors were identified to relate to sarcopenia and aging traits causally, and most were associated with only one outcome trait. IL16 (interleukin‐16), CTACK (cutaneous T‐cell attracting chemokine), MIP1b (macrophage inflammatory protein 1b) and PDGFbb (platelet‐derived growth factor BB) were proven to relate causally to at least one sarcopenia and aging trait in both analyses with two significance thresholds. IL16 was causally associated with hand grip strength (0.977 [0.956–0.998] for EWGSOP and 0.933 [0.874–0.996] for FNIH), AALM (0.991 [0.984, 0.998]), MVPA (0.997 [0.995–1.000]) and AWCU10 (1.008 [1.003–1.013]). CTACK was proven to relate causally to hand grip strength (1.013 [1.007–1.019] for EWGSOP and 1.090 [1.041–1.142] for FNIH), AWCU10 (0.990 [0.986–0.994]) and telomere length (0.998 [0.983–0.994]). The results indicated that MIP1b has a causal effect on hand grip strength (1.032 [1.001–1.063] for EWGSOP), AWCU10 (0.994 [0.988–1.000] and 0.993 [0.988–0.998]) and telomere length (1.006 [1.000–1.012]). PDGFbb may causally relate to AALM (1.016 [1.001–1.030]) and telomere length (1.011 [1.007–1.015]). Reserve MR analyses also proved their unidirectional causal effects.ConclusionsTwenty‐seven factors were causally related to sarcopenia and aging traits, and the causal effects of IL16, CTACK, MIP1b and PDGFbb were proven in both analyses with two significance thresholds.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mapping the causal associations of cytokines with sarcopenia and aging traits: Evidence from bidirectional Mendelian randomization

Liu,

Fu,

et al. 2024

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

show abstract

Regulation of Cellular Processes by Interleukin‐16 in Homeostasis and Cancer

Richmond

Tuzova

Cruikshank

2013

Journal Cellular Physiology

133

View full text Add to dashboard Cite

Interleukin-16 (IL-16) is generated as a precursor molecule that is cleaved by caspase-3 to produce a pro-IL-16 molecule that functions as a regulator of T cell growth, and a secreted peptide that functions as a CD4 and/or CD9 ligand for induction of cell motility and activation. IL-16 has been predominantly studied as a contributing factor in the orchestration of an immune response; however, more recently IL-16 bioactivity has been closely associated with the progression of a number of different cancers. While the association between IL-16 plasma levels and tumor progression has been reported for many types of cancer, the mechanism for IL-16 involvement has been partially elucidated for three of the cancer types, cutaneous T cell lymphoma (CTCL), multiple myeloma (MM), and breast cancer. The mechanism for promoting cell growth is different in each of these cancers and involves a sequence mutation in the pro-molecule facilitating decreased p27(KIP1) levels in CTCL; over expression of the secreted IL-16 molecule to induce proliferation in CTCL T cells, and plasma cells in MM; and increased secreted IL-16 acting to recruit CD4+ pro-tumor macrophages in breast cancer. This article will review the cellular process for generating IL-16, the biological activities for both the pro- and secreted forms of the protein, and then the mechanism by which these forms contribute to cancer progression. As a soluble cytokine the ability to reduce or eliminate IL-16 synthesis through siRNA approaches or bioactivity through the use of neutralizing antibody treatment may represent a novel therapeutic approach.

show abstract

Anti‐IL‐16 therapy reduces CD4+ T‐cell infiltration and improves paralysis and histopathology of relapsing EAE

Skundric

Dai

Zakarian

et al. 2005

J of Neuroscience Research

View full text Add to dashboard Cite

Infiltration of the central nervous system (CNS) by CD4+ Th1 cells precedes onset and relapses of experimental autoimmune encephalomyelitis (EAE). We reported that (B6xSJL) F1 (H-2b/s) mice with severe relapsing-remitting disease had extensive infiltration by CD4+ T cells compared to that in C57BL/6 (B6) (H-2b) mice, which developed mild low-relapsing disease in response to myelin oligodendrocyte peptide 35-55 (MOG(35-55)). This observation led us to search for mechanisms that specifically regulate trafficking of CD4+ cells in relapsing H-2b/s mice. We show that the CD4+ cell chemoattractant cytokine interleukin (IL)-16 has an important role in regulation of relapsing EAE induced by MOG(35-55) in the (B6xSJL) F1 (H-2b/s) mice. We found production of IL-16 in the CNS of mice with EAE. IL-16 levels in the CNS correlated well with the extent of CD4+ T-cell and B-cell infiltration during acute and relapsing disease. Infiltrating CD4+ T cells, B cells, and to a lesser extent CD8+ T cells all contained IL-16 immunoreactivity. Treatment with neutralizing anti-IL-16 antibody successfully reversed paralysis and ameliorated relapsing disease. In treated mice, diminished infiltration by CD4+ T cells, less demyelination, and more sparing of axons was observed. Taken together, our results show an important role for IL-16 in regulation of relapsing EAE. We describe a novel therapeutic approach to specifically impede CD4+ T cell chemoattraction in EAE based on IL-16 neutralization. Our findings have high relevance for the development of new therapies for relapsing EAE and potentially MS.

show abstract

Reciprocal Desensitization of CCR5 and CD4 Is Mediated by IL-16 and Macrophage-Inflammatory Protein-1β, Respectively

Cited by 43 publications

References 36 publications

Mapping the causal associations of cytokines with sarcopenia and aging traits: Evidence from bidirectional Mendelian randomization

Mapping the causal associations of cytokines with sarcopenia and aging traits: Evidence from bidirectional Mendelian randomization

Regulation of Cellular Processes by Interleukin‐16 in Homeostasis and Cancer

Anti‐IL‐16 therapy reduces CD4+ T‐cell infiltration and improves paralysis and histopathology of relapsing EAE

Contact Info

Product

Resources

About