scholarly journals T Helper Type 17 Immune Response Plays an Indispensable Role for Development of Iodine-Induced Autoimmune Thyroiditis in Nonobese Diabetic-H2h4 Mice

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 5135-5142 ◽  
Author(s):  
Ichiro Horie ◽  
Norio Abiru ◽  
Yuji Nagayama ◽  
Genpei Kuriya ◽  
Ohki Saitoh ◽  
...  

T helper type 1(Th1)/Th2 paradigm has been expanded by discovery of a novel effector T cell (Teff) subset, Th17 cells, which produce a proinflammatory cytokine IL-17. Th17 cells have recently been shown to play a major role in numerous autoimmune diseases that had previously been thought to be Th1-dominant diseases. We here studied the significance of Th17 cells in iodine-induced autoimmune thyroiditis in nonobese diabetic-H2h4 mice, a mouse model of Hashimoto’s thyroiditis in humans, which spontaneously develop antithyroglobulin autoantibodies and intrathyroidal lymphocyte infiltration when supplied with iodine in the drinking water. We observed increased numbers of Th1 and Th17 cells in spleen and accumulation of both types of Teff in the thyroid glands of iodine-fed wild-type mice, indicating that Th17 cells as well as Th1 cells constitute thyroid lesions. Furthermore, the incidence and severity of intrathyroidal lymphocyte infiltration, and the titers of antithyroglobulin autoantibodies were markedly reduced in iodine-treated IL-17−/− mice as compared with wild-type mice. Of interest, IL-17+/− mice showed an intermediate phenotype. Therefore, the present study, together with a previous report demonstrating the importance of Th1, not Th2, immune response for developing thyroiditis using mice deficient for interferon-γ or IL-4, clearly indicates that both Th1 and Th17 cells are critical Teff subsets for the pathogenesis of spontaneous autoimmune thyroiditis in nonobese diabetic-H2h4 mice.

2009 ◽  
Vol 30 (6) ◽  
pp. 748-748
Author(s):  
Ichiro Horie ◽  
Norio Abiru ◽  
Yuji Nagayama ◽  
Genpei Kuriya ◽  
Ohki Saitoh ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xiang-Tian Meng ◽  
Yun-Yue Shi ◽  
Hong Zhang ◽  
Hong-Yan Zhou

Allergic conjunctivitis (AC) is a common allergic disease that is often associated with the onset of rhinitis or asthma. The incidence of AC has increased significantly in recent years possibly due to air pollution and climate warming. AC seriously affects patients’ quality of life and work efficiency. Th (T-helper) 2 immune responses and type I hypersensitivity reactions are generally considered the basis of occurrence of AC. It has been found that new subpopulations of T-helper cells, Th17 cells that produce interleukin-17 (IL-17), play an important role in the Th2-mediated pathogenesis of conjunctivitis. Studies have shown that Th17 cells are involved in a variety of immune inflammation, including psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. However, the role of Th17 and IL-17 in AC is unclear. This paper will focus on how T-helper 17 cells and interleukin-17 are activated in the Th2 immune response of allergic conjunctivitis and how they promote the Th2 immune response of AC.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2299-2299
Author(s):  
Dingyan Wang ◽  
A. Keith Stewart ◽  
Lihua Zhuang ◽  
Nancy Xiao ◽  
Mawmaw Hlaing ◽  
...  

Abstract HACS1 is a SH3 (Src homology 3) and SAM (sterile alpha motif) domain containing adaptor protein that is expressed in activated B and dendritic cells, is up-regulated by Interleukin 4 in the process of B cell activation and likely serves to dampen the immune response. To elucidate the function of HACS1, we generated HACS1 gene knockout mice by deletion of the SH3 and SAM domains. HACS1−/− mice were viable and fertile and had normal bone marrow B cell development and normal splenic T and B cell populations. However, adult HACS1−/− mice had increased numbers of peritoneal B1 cells (IgM+CD5+). Upon LPS plus BCR or TCR stimulations, splenic cells from HACS1−/− mice demonstrated an upregulation of activation markers with increased intensity of CD23 expression or increased population of CD69 positive cells. Purified B220+ splenic B cells from HACS1−/− mice showed increased cell proliferation upon BCR stimulation. Both T helper type 1 (Th1) and T helper type 2 (Th2) humoral responses were enhanced in HACS1−/− mice upon immunization with T cell-dependent antigen NP-KLH, which resulted in increased production of interferon-gamma (IFN-γ), anti-NP IgG2a and IL-4, as well as anti-NP IgG1 and IgE. Upon immunization with T cell-independent antigens such as TNP-LPS and TNP-Ficoll, HACS1−/− mice had increased production of anti-TNP IgM and IgG3 as compared to normal controls. The in vitro maturation of bone marrow-derived dentritic cells from HACS1−/− mice was similar to wild-type mice but HACS1−/− dentritic cells showed increased IL-12 production upon stimulation with anti-CD40 or LPS. There was no significant difference in antigen uptake by cultured dentritic cells from non-immunized wild-type or knockout mice. However, in immunized mice, an increase in antigen uptake in HACS1−/− dentritic cells was observed. We further demonstrate that the HACS1−/− B cells had increased tyrosine phosphorylation in the resting state. As deletion of the SH3 & SAM domains of HACS1 appears to generate a hypersensitive immune response, our results collectively support that HACS1 negatively regulates adaptive immunity.


Cytokine ◽  
2010 ◽  
Vol 52 (1-2) ◽  
pp. 82
Author(s):  
Aurelio Flores-Garcı´a ◽  
Vicente Garibaldi-Becerra ◽  
Martha Barba-Barajas ◽  
Jesus S. Velarde-Félix ◽  
Luis E. Wong-Ley-Madero ◽  
...  

2022 ◽  
Vol 12 ◽  
Author(s):  
Shigeki Katoh

Interactions between CD44 and hyaluronan (HA) are crucial for recruiting leukocytes to inflamed tissues. This review summarizes findings from our studies of the roles of CD44-HA interactions in leukocyte trafficking, with a particular focus on airway T helper type 2 (Th2) cells in mouse models of acute asthma. In a mite allergen-induced model of acute asthma, intraperitoneal injection of anti-CD44 monoclonal antibodies blocked lymphocytes and eosinophils from accumulating in the lung, and suppressed both the antigen-induced increase in Th2 cytokines in the bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR). CD44 deficiency was associated with decreased mite allergen-induced Th2 cell-mediated airway inflammation and AHR in sensitized mice. Asthmatic responses to antigen-sensitized splenic CD4+ T cells transferred from CD44-deficient mice were weaker than in wild-type mice. Administration of anti-CD44 monoclonal antibodies preferentially suppressed the airway accumulation of antigen-specific Th2 cells induced by antigen challenge, without affecting Th1 and Th17 cells. Increased HA-binding ability of CD44 and expression of Neu1 sialidase were observed on antigen-specific Th2 cells compared with antigen-specific Th1 and Th17 cells. Finally, in a mouse model of acute asthma, neuraminidase 1-deficient SM/J mice exhibited a lower Th2 cytokine concentration and a lower absolute Th2 cell number in the BALF, as well as an attenuated AHR. Our findings indicate that CD44 critically contributes to the antigen challenge-induced airway accumulation of antigen-specific Th2 cells, without affecting Th1 and Th17 cells, in mice. Furthermore, neuraminidase 1 activity is necessary for the interaction between HA and CD44, and Th2 cell-mediated airway inflammation.


2000 ◽  
Vol 113 (20) ◽  
pp. 3549-3550
Author(s):  
M.J. Townsend ◽  
A.N. McKenzie

The Cytokine Network edited by Fran Balkwill Frontiers in Molecular Biology Series (seried editors B. D. Hames and D. M. Glover) Oxford University Press (2000) pp. 199. ISBN 019–963-702-4. 29.95 Cytokines are small- to medium-sized proteins and glycoproteins that mediate highly potent biological effects on many cell types. They have critical roles in haematopoiesis, inflammatory responses and the development and maintenance of immune responses. Importantly, cytokines act in networks or cascades. Typical properties of cytokines in these networks are pleiotropy, redundancy, synergistic activity and antagonistic effects upon each other. Knowledge of how these networks are comprised and operate is important in understanding how cytokines mediate their diverse effects on biological systems. In The Cytokine Network, Fran Balkwill brings together some distinguished investigators to produce a survey, in eight independently written and concise chapters, of the complex cytokine and chemokine (chemotactic cytokine) networks present in mouse and man. The ever-increasing complexity of cytokine networks is introduced in the initial chapter with a summary of the bioinformatics approach for the high throughput discovery of novel cytokines and chemokines. The burgeoning number of newly identified chemokines, chemokine receptors and TNF family members reminds us that our understanding of the cytokine network is extremely dynamic and that our interpretation of some pathways will change with the characterisation of new factors. The following chapters address the interactions of the cytokines, both with reference to their signalling pathways (well summarised in chapter 2) and their biological roles. The point is made that cytokines should be studied as a network rather than individually and that in vivo models, including the generation of transgenic and gene knock-out mice, are powerful tools for doing so. Rheumatoid arthritis is presented as a well-studied example of how inappropriate regulation of pro- and anti-inflammatory cytokines mediates autoimmune disease, and examples of immunoregulatory cytokines that have both overlapping and independent regulatory effects on inflammation are demonstrated within this context. The important Th1/Th2 paradigm receives a dedicated chapter. T helper type 1 and T helper type 2 cells produce distinct and restricted patterns of cytokines that cross regulate each other and thus mediate different types of immune response. The development of these subsets of T helper cells from a common precursor, as part of a developing immune response, has important effects on the cytokine network. The mechanisms of Th1/Th2 development together with modulating factors and associated intracellular signalling are well described. The chapter summarises well the role of Th1/Th2 development in human diseases with reference to transplantation immunology, neonatal development, autoimmune diseases, and atopic diseases. A very interesting review of the relationships between cytokines and viruses is given. Cytokines are critically involved in mediating antiviral immune responses. However, homologues of cytokines, chemokines and their receptors, after being ‘hijacked’ from the host genome and undergoing evolution along with the viral genes, are utilised by viruses themselves to promote their replication and to suppress immune responses against them. The chapter describes several noteworthy examples of these virally encoded cytokines and receptors together with their roles in vivo. This is a well-written book that provides a good introduction to understanding how cytokines and chemokines interact as a network in the immune system. The volume links together diverse subjects that include cytokine signalling, genomic polymorphism, disease processes and immunotherapies. The book does not aim to describe comprehensively the biology of all the currently known cytokines and chemokines and therefore alternative texts should be considered for this. (ABSTRACT TRUNCATED)


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