scholarly journals Leukocyte Localization in a Model of Innate Immune-Driven Colitis

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Jordan R. Jones ◽  
Anne-Marie C. Overstreet ◽  
Antonia M. Boger-May ◽  
David L. Boone
Keyword(s):  
Immune Cell ◽  
Cell Subset ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
T Helper Cell ◽  
Cell Surface Markers ◽  
T Helper ◽  
Immune Cell Subset ◽  
Inflammatory State ◽  
Inflammatory Bowel

Background and Hypothesis:  Inflammatory bowel disease (IBD) is a disabling, chronic gut disorder involving immune dysregulation. Our lab has generated a murine IBD model in which the innate immune system drives inflammation. Innate lymphoid cells (ILCs), an innate immune cell subset that was recently discovered, exhibit many T-helper cell characteristics. ILCs, though few, produce cytokines, thereby significantly impacting tissue through local action in mucosal sites. They express the cell surface markers, CD90, which is unique to ILCs, and CD45, which all leukocyte types express. Colitis prevention in our model via ILC depletion indicates a role for ILCs in IBD. Therefore, we aimed to identify the ILCs’ localization in our murine model. We hypothesized that the ILCs will localize to inflamed areas of the intestinal lamina propria and into the intraepithelial spaces.  Experimental Design or Project Methods:  Mice expressing TNFAIP3, an inhibitor of NF-kB, were mated with adaptive immunity-lacking mice (RAG1-/-). RAG1-/- x Villin-TNFAIP3 (TRAG) mice had colitis that was 100% penetrant by age 6 weeks. Distal colons excised at age 4 weeks and 8 weeks were used for identifying CD45+ and CD90+ cells in both RAG and TRAG mice intestines via immunofluorescence.  Results:  We observed differences in the distributions of CD90+ and CD45+ cells within TRAG and RAG mice intestines.  Conclusion and Potential Impact:  Differences exist in intestinal leukocyte distributions within our models. Altered ILC distribution might reflect an inflammatory state or contribute to IBD pathology. This work may further elucidate ILCs’ role in IBD and as IBD treatment targets.

scholarly journals CD4 T Helper Cell Subsets and Related Human Immunological Disorders

2020 ◽  
Vol 21 (21) ◽  
pp. 8011 ◽  
Author(s):  
Xiaoliang Zhu ◽  
Jinfang Zhu
Keyword(s):  
Transcription Factor ◽  
Immune System ◽  
Immune Responses ◽  
Critical Role ◽  
Cell Subset ◽  
Lymphoid Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
Th2 Cells ◽  
T Helper

The immune system plays a critical role in protecting hosts from the invasion of organisms. CD4 T cells, as a key component of the immune system, are central in orchestrating adaptive immune responses. After decades of investigation, five major CD4 T helper cell (Th) subsets have been identified: Th1, Th2, Th17, Treg (T regulatory), and Tfh (follicular T helper) cells. Th1 cells, defined by the expression of lineage cytokine interferon (IFN)-γ and the master transcription factor T-bet, participate in type 1 immune responses to intracellular pathogens such as mycobacterial species and viruses; Th2 cells, defined by the expression of lineage cytokines interleukin (IL)-4/IL-5/IL-13 and the master transcription factor GAΤA3, participate in type 2 immune responses to larger extracellular pathogens such as helminths; Th17 cells, defined by the expression of lineage cytokines IL-17/IL-22 and the master transcription factor RORγt, participate in type 3 immune responses to extracellular pathogens including some bacteria and fungi; Tfh cells, by producing IL-21 and expressing Bcl6, help B cells produce corresponding antibodies; whereas Foxp3-expressing Treg cells, unlike Th1/Th2/Th17/Tfh exerting their effector functions, regulate immune responses to maintain immune cell homeostasis and prevent immunopathology. Interestingly, innate lymphoid cells (ILCs) have been found to mimic the functions of three major effector CD4 T helper subsets (Th1, Th2, and Th17) and thus can also be divided into three major subsets: ILC1s, ILC2s, and ILC3s. In this review, we will discuss the differentiation and functions of each CD4 T helper cell subset in the context of ILCs and human diseases associated with the dysregulation of these lymphocyte subsets particularly caused by monogenic mutations.

scholarly journals P060 The pharmacologic inhibition of store-operated calcium entry pathway in inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S164-S165
Author(s):  
M Letizia ◽  
C Yerinde ◽  
A Sand ◽  
S Schlickeiser ◽  
U Kaufmann ◽  
...  
Keyword(s):  
T Cells ◽  
Lamina Propria ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Cell Subset ◽  
Mass Cytometry ◽  
Immune Cell Subset ◽  
Store Operated Calcium Entry ◽  
Inflammatory Bowel ◽  
And Function

Abstract Background Store-operated calcium entry (SOCE) represents the major calcium influx pathway in T cells which not only controls the activation and function of lymphocytes, but which also has been implicated in the metabolic homeostasis and survival of murine CD4+ and CD8+ T cells. Conditional knockout mice, in which SOCE signalling components are deleted in T cells, revealed that SOCE is required for the induction of intestinal inflammation in mouse models of colitis. However, the effects of SOCE inhibition have not been studied in inflammatory bowel disease (IBD) and it remains elusive, which immune cell subset is affected by the pharmaceutical blockade of SOCE. We therefore aim to investigate the effects of SOCE inhibitor BTP-2 on functions and metabolic homeostasis of human lymphocytes isolated from IBD patients. Methods PBMC and/or lamina propria lymphocytes were isolated from colitis patients undergoing colon resection and mass cytometry served in order to evaluate the cytokine production and activation of B, T, NK as well as myeloid cells. Additionally, Ca2+ influx measurement and Seahorse analyses were performed in order to assess the metabolic status of immune cell subsets after SOCE inhibition. Results Data on B, T, NK, myeloid cells and neutrophils isolated from peripheral blood or colon lamina propria revealed that each immune cell subset harbours a distinctive SOCE-dependent Ca2+ influx rate, suggesting that SOCE might differentially regulate the activation and function of each cell subtype. In particular, CD4+ and CD8+ T cells, B and NK cells as well as monocytes were highly susceptible to extracellular Ca2+ influx, followed by granulocytes. Furthermore, inhibition of SOCE in lymphocytes resulted in impaired metabolic fitness, reduced glycolytic capacity and impaired fatty acid oxidation. Finally, BTP-2 was able to decrease the production of key pro-inflammatory cytokines involved in IBD, including TNFα and IL-17 in lamina propria resident T cells. Conclusion Our data revealed for the first time that the cytokine production and the activation of several immune cell subtypes can be modulated by SOCE blockade in human intestinal inflammation, identifying SOCE as a novel therapeutic target in colitis. Moreover, we hope that a wide phenotypical characterisation of immune cells via mass cytometry will provide a better insight into positive as well as negative effects of SOCE inhibitors that might interfere with the clinical applicability of SOCE inhibitors for treating IBD.

scholarly journals Generation of IL-8 and IL-9 Producing CD4+T Cells Is Affected by Th17 Polarizing Conditions and AHR Ligands

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Michaela Gasch ◽  
Tina Goroll ◽  
Mario Bauer ◽  
Denise Hinz ◽  
Nicole Schütze ◽  
...  
Keyword(s):  
T Cells ◽  
T Helper Cells ◽  
Th17 Cells ◽  
Immune Cell ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Helper Cells ◽  
Aryl Hydrocarbon

The T helper cell subsets Th1, Th2, Th17, and Treg play an important role in immune cell homeostasis, in host defense, and in immunological disorders. Recently, much attention has been paid to Th17 cells which seem to play an important role in the early phase of the adoptive immune response and autoimmune disease. When generating Th17 cells underin vitroconditions the amount of IL-17A producing cells hardly exceeds 20% while the nature of the remaining T cells is poorly characterized. As engagement of the aryl hydrocarbon receptor (AHR) has also been postulated to modulate the differentiation of T helper cells into Th17 cells with regard to the IL-17A expression we ask how far do Th17 polarizing conditions in combination with ligand induced AHR activation have an effect on the production of other T helper cell cytokines. We found that a high proportion of T helper cells cultured under Th17 polarizing conditions are IL-8 and IL-9 single producing cells and that AHR activation results in an upregulation of IL-8 and a downregulation of IL-9 production. Thus, we have identified IL-8 and IL-9 producing T helper cells which are subject to regulation by the engagement of the AHR.

scholarly journals Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis

Nature ◽  
2017 ◽  
Vol 542 (7639) ◽  
pp. 110-114 ◽  
Author(s):  
Deepak A. Rao ◽  
Michael F. Gurish ◽  
Jennifer L. Marshall ◽  
Kamil Slowikowski ◽  
Chamith Y. Fonseka ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
Cell Subset ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Helper Cell Subset

scholarly journals IL-17+ Mast Cell/T Helper Cell Axis in the Early Stages of Acne

2021 ◽  
Vol 12 ◽  
Author(s):  
Yoan Eliasse ◽  
Edouard Leveque ◽  
Lucile Garidou ◽  
Louise Battut ◽  
Brienne McKenzie ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cell ◽  
Mast Cells ◽  
Immune Cell ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Cell Axis ◽  
Early Stages ◽  
Cutibacterium Acnes

Acne is a multifactorial disease driven by physiological changes occurring during puberty in the pilosebaceous unit (PSU) that leads to sebum overproduction and a dysbiosis involving notably Cutibacterium acnes. These changes in the PSU microenvironment lead to a shift from a homeostatic to an inflammatory state. Indeed, immunohistochemical analyses have revealed that inflammation and lymphocyte infiltration can be detected even in the infraclinical acneic stages, highlighting the importance of the early stages of the disease. In this study, we utilized a robust multi-pronged approach that included flow cytometry, confocal microscopy, and bioinformatics to comprehensively characterize the evolution of the infiltrating and resident immune cell populations in acneic lesions, beginning in the early stages of their development. Using a discovery cohort of 15 patients, we demonstrated that the composition of immune cell infiltrate is highly dynamic in nature, with the relative abundance of different cell types changing significantly as a function of clinical lesion stage. Within the stages examined, we identified a large population of CD69+ CD4+ T cells, several populations of activated antigen presenting cells, and activated mast cells producing IL-17. IL-17+ mast cells were preferentially located in CD4+ T cell rich areas and we showed that activated CD4+ T cells license mast cells to produce IL-17. Our study reveals that mast cells are the main IL-17 producers in the early stage of acne, underlying the importance of targeting the IL-17+ mast cell/T helper cell axis in therapeutic approaches.

Biologicals targeting T helper cell subset differentiating cytokines are effective in the treatment of murine anti-myeloperoxidase glomerulonephritis

2019 ◽  
Vol 96 (5) ◽  
pp. 1121-1133 ◽  
Author(s):  
Poh-Yi Gan ◽  
Amy Chan ◽  
Joshua D. Ooi ◽  
Jonathan Dick ◽  
Kei Nagai ◽  
...  
Keyword(s):  
Cell Subset ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Helper Cell Subset

scholarly journals Hapten-induced Colitis Is Associated with Colonic Patch Hypertrophy and T Helper Cell 2–Type Responses

1999 ◽  
Vol 189 (8) ◽  
pp. 1169-1180 ◽  
Author(s):  
Taeko Dohi ◽  
Kohtaro Fujihashi ◽  
Paul D. Rennert ◽  
Koichi Iwatani ◽  
Hiroshi Kiyono ◽  
...  
Keyword(s):  
Sulfonic Acid ◽  
Intestinal Inflammation ◽  
T Helper Cell ◽  
Trinitrobenzene Sulfonic Acid ◽  
Murine Models ◽  
T Helper ◽  
Mucosal Layer ◽  
Inflammatory Bowel ◽  
Ifn Γ ◽  
Tnbs Colitis

To investigate the potential involvement of T helper (Th)2-type responses in murine models of intestinal inflammation, we used trinitrobenzene sulfonic acid (TNBS)–hapten to induce inflammatory bowel disease in situations where Th1-type responses with interferon (IFN)-γ synthesis are either diminished or do not occur. Intracolonic administration of TNBS to either normal (IFN-γ+/+) or Th1-deficient IFN-γ knockout (IFN-γ−/−) BALB/c mice resulted in significant colitis. In IFN-γ−/− mice, crypt inflammation was more severe than in IFN-γ+/+ mice and was accompanied by hypertrophy of colonic patches with a lymphoepithelium containing M cells and distinct B and T cell zones resembling Peyer's patches. Hapten-specific, colonic patch T cells from both mouse groups exhibited a Th2 phenotype with interleukin (IL)-4 and IL-5 production. TNBS colitis in normal mice treated with anti–IL-4 antibodies or in IL-4−/− mice was less severe than in either IFN-γ+/+ or IFN-γ−/− mice. Our findings now show that the Th2-type responses in TNBS colitis are associated with colonic patch enlargement and inflammation of the mucosal layer and may represent a model for ulcerative colitis.

scholarly journals Maturation of Lymphocyte Immunophenotypes and Memory T Helper Cell Differentiation During Development in Mice

2000 ◽  
Vol 8 (1) ◽  
pp. 47-60 ◽  
Author(s):  
Omar R. Fagoaga ◽  
Steven. M. Yellon ◽  
Sandra. L. Nehlsen-Cannarella
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cell Differentiation ◽  
B Cells ◽  
Cell Subset ◽  
T Helper Cell ◽  
Natural Killers ◽  
Memory Cells ◽  
Spleen Lymphocyte ◽  
T Helper

The goal of this study was to systematically investigate the ontogeny of lymphoid populations throughout postnatal development. In CD-1 mice, peak lymphocyte numbers occurred in blood on postnatal day 10 (dl0) including those for natural killers (NK1.1), B cells (CD19), T helper (CD3CD4), naïve T helper (CD4CD62LposCD44low), memory T helper (CD4CD62LnegCD44high), and T cytotoxic (CD3CD8) cells. As percent of total lymphocytes, peaks were achieved by d10 for all T helper subtypes but not B cells which declined to a nadir. In spleen, lymphocyte numbers increased exponentially after d10. Proportionately, NK and T cells peaked on d10, declined by d20, and increased 2–3-fold by d45. Naive T cells constituted the majority of lymphocytes during development while memory cells gained to 2.2% (blood) and 12 % (spleen) by d20. C57BL/6 mice had similar profiles except that the B cell nadir and T cell subset peaks were at d5. Peripheralization of critical numbers of lymphocytes by d10, and importantly, development of a repertoire of memory cells by d20, may define immune response capabilities that close the period of immaturity for the neonate.

scholarly journals Quantitative Analysis of Immune Cell Subset Infiltration of Supraspinatus Muscle After Severe Rotator Cuff Injury

2017 ◽  
Vol 3 (2) ◽  
pp. 82-93 ◽  
Author(s):  
J. R. Krieger ◽  
L.E. Tellier ◽  
M.T. Ollukaren ◽  
J.S. Temenoff ◽  
E.A. Botchwey
Keyword(s):  
Quantitative Analysis ◽  
Rotator Cuff ◽  
Immune Cell ◽  
Cell Subset ◽  
Immune Cell Subset ◽  
Supraspinatus Muscle ◽  
Rotator Cuff Injury
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